Dystrophia Myotonica 1; Steinert’s Disease

Myotonic dystrophy type 1 (DM1) is a disorder of smooth and skeletal muscle that also affects the eye, heart, endocrine system, and central nervous system. The clinical continuum has been divided into roughly three categories: mild (cataract and myotonia), classic (muscle weakness and wasting, myotonia, cataract and, often, cardiac conduction abnormalities), and congenital (severe hypotonia and severe generalized weakness at birth, often with respiratory insufficiency and, frequently, intellectual disability).

DM1 is caused by an increased number of CTG trinucleotide repeats in the 3′ untranslated region of the DMPK gene. The inheritance pattern is autosomal dominant with anticipation. Anticipation is the phenomenon of increased severity or decreased age of onset in successive generation due to expansion of the unstable repeat. In DM1, anticipation is typically greater with maternal transmission of the expanded allele.

DMPK alleles are classified as:

• Normal: 5 to 34 CTG repeats
• Mutable Normal: 35 to 49 repeats
  These alleles are not disease-causing, but may be at risk of expansion into the pathogenic range in subsequent generations.
• Full Penetrance: >50 repeats

In general, longer CTG repeat expansions correlate with an earlier age of onset and more severe disease; however, there is overlap in the repeat ranges associated with the categories of clinical presentation. Individuals with mild DM1 typically have between 50 and ~150 repeats; those with classic DM1 typically have between ~100 to ~1000; and, those with congenital DM1 typically have >1000 repeats. Most often, a child with congenital DM1 has inherited the expanded DMPK allele from the mother. Although expansion into the disease-causing range typically occurs in maternal transmission, paternal inheritance has been described.

1. Confirmation of diagnosis:
   1. In individuals with clinical features suggestive of myotonic dystrophy.
2. Prenatal testing (prenatal diagnosis requests are not normally accepted from physicians other than Medical Geneticists):
   1. Pregnancies at risk of myotonic dystrophy type 1 because of a history of molecularly confirmed DM1 in one parent.
3. Presymptomatic testing:
   1. Adults known to be at risk of myotonic dystrophy type 1 because of a molecularly confirmed family history of the condition.

PCR and triplet-primed (tp) PCR amplification is performed across the CTG repeat region of the DMPK gene to assess for expansion.  Sizing is performed up to ~100 repeats; sizing beyond 100 repeats is not possible with this assay.    

In rare cases, a repeat collection and testing by Southern blot analysis will be recommended.

For more information, see FAQ

Pregnancy-related/Prenatal

If pregnancy management will be altered, 3 weeks; otherwise, routine TAT.

Blood: 4 mL EDTA is optimal (Minimum: 1 mL EDTA)
DNA: 100 μL at 200 ng/μL is optimal (Minimum: 30 μL at 200 ng/μL)

Label each sample with three patient identifiers; preferably patient name, PHN, and date of birth and ship to the address below. Samples should be shipped at room temperature with a completed MGL Requisition to arrive Monday to Friday (not on Canadian statutory holidays).  

Prenatal Specimens
Prenatal testing REQUIRES LABORATORY CONSULTATION PRIOR TO THE PROCEDURE and can only be ordered by a Medical Geneticist. Contact the laboratory at 604-875-2852 and choose the appropriate option for the Molecular Geneticist on service.
Chorionic Villi: 20 mg.
Direct Amniotic fluid: 25 mL collected in two separate tubes of equal volume.
Cultured Amniocytes: Two (2) 100% confluent T-25 flasks.
DNA extracted from prenatal specimens: 100 μL at 200 ng/μL is optimal (Minimum: 30 μL at 200 ng/μL)

Label each sample with three patient identifiers; preferably patient name, PHN, and date of birth. Ship samples by overnight courier with a completed MGL Requisition to arrive Monday to Friday (not on Canadian statutory holidays) as follows:

• Villi – on wet ice or in media at room temperature
• Amniocytes, Amniotic fluid, DNA – at room temperature

Testing is only available to residents of Canada, except in very specific circumstances where testing is urgent or emergent.  Payment is not required when requests are made for individuals who are insured by Health Insurance BC (administered through the BC Medical Services Plan (MSP)) AND eligible for testing according to the test utilization guidelines / policy. If the individual undergoing testing is not insured by these providers or does not meet utilization guidelines or policy, please complete a billing form; testing will only commence after receipt of billing informationTest prices can be found here.

For carrier/predictive testing due to family history, it is generally important to first document the gene mutation in an affected or carrier family member.  Ideally, this information should be provided to the laboratory for assessment of whether the assay is appropriate for detection of the familial mutation, and to aid in the interpretation of data.

In certain scenarios of repeat size mosaicism, false negative results may occur.  If results obtained do not match the clinical findings, consult the on-service Molecular Geneticist.

Rare single nucleotide variants or polymorphisms could lead to false-negative results. If results obtained do not match the clinical findings, consult the on-service Molecular Geneticist.

A previous bone marrow transplant from an allogenic donor will result in molecular data that reflects the donor genotype rather than the recipient (patient) genotype.  Consult the on-service Molecular Geneticist for approach to testing in such individuals. 

Transfusions performed with packed red blood cells will generally not affect the outcome of molecular genetic testing.  However, if there is no clinical urgency, the cautious approach is to wait one week post-packed red cell transfusion before collecting a sample for genetic testing.  Consult the on-service Molecular Geneticist as needed.

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.

Duchenne Muscular Dystrophy; Becker Muscular Dystrophy; DMD-Related Dilated Cardiomyopathy

The dystrophinopathies manifest as a spectrum of muscle diseases. The mildest of the phenotypes includes an asymptomatic increase in serum concentration of creatine phosphokinase (CK or CpK), muscle cramps with myoglobinuria, and isolated quadriceps myopathy. At the opposite end of the spectrum is Duchenne muscular dystrophy (DMD), usually presenting in early childhood with delay in the motor milestones. DMD is rapidly progressive; patients are usually wheelchair-bound by 12 years of age and death usually occurs before age 30, due most frequently to respiratory complications and/or cardiomyopathy. Becker muscular dystrophy (BMD) is characterized by later-onset skeletal muscle weakness; individuals with BMD usually remain ambulatory well into their 20s. Despite the milder skeletal muscle involvement in BMD, cardiomypathy is a common cause of morbidity and the most common cause of death (on average in the mid-40s). Finally, DMD-associated dilated cardiomyopathy (DCM) is characterized by left ventricular dilation and congestive heart failure. Female carriers of DMD mutations are at increased risk for cardiomyopathy.

The dystrophinopathies are due to mutations in dystrophin (DMD), an X-linked gene encoding a membrane-associated protein that is found in muscle and a subset of neurons. The Duchenne phenotype is almost invariably caused by mutations that disrupt the reading frame including: deletions or duplications; nonsense mutations, and splice-site mutations. These produce a dystrophin protein molecule that is degraded. The milder Becker phenotype, on the other hand, results from mutations that reduce but do not completely eliminate the production of functional dystrophin protein, including deletions or duplications that maintain the open reading frame of the transcript, some splicing mutations, and most non-truncating single-base changes that result in translation of a protein product with intact N and C termini. DMD-associated dilated cardiomyopathy is caused by mutations in DMD that affect the muscle promoter (PM) and the first exon (E1), resulting in no dystrophin transcript being produced in cardiac muscle; expression (under different promoters) is retained in skeletal muscle and the central nervous system.

1. Confirmation of diagnosis:
   1. Testing of males with a suspected diagnosis of DMD.
   2. Testing of females is warranted if there is a clinical presentation consistent with the disease.
2. Carrier testing:
   1. Testing of adult females at risk to be carriers because of a family history. NB: Carriers have the potential for health problems in addition to the ability to transmit disease to offspring; genetic counselling is recommended prior to testing.
3. Prenatal testing (prenatal diagnosis requests are not normally accepted from physicians other than Medical Geneticists):
   1. Pregnancies at risk of inheriting a known DMD deletion or duplication. Prior to testing for the DMD mutation, fetal sexing is performed; if the fetus is female, further testing is not indicated.
      NB: If the mutation segregating in the mother is not known, consult the on-service Molecular Geneticist for assessment of whether linkage analysis is available for prenatal diagnosis
4. Presymptomatic testing:
   1. Requests for presymptomatic testing are only accepted following genetic counselling by a recognized genetic service.

Multiplex ligation-dependant probe amplification (MLPA) is carried out with the P034-A2 and P035-A2 probe mixes (MRC-Holland) to detect whole exon deletions and duplications; each of the 79 exons of DMD and the alternate exon 1 (DP427c) are assessed.

Pregnancy-related/Prenatal

If pregnancy management will be altered, 3 weeks; otherwise, routine TAT.

Blood: 4 mL EDTA is optimal (Minimum: 1 mL EDTA)
DNA: NOT ACCEPTED

Label each sample with three patient identifiers; preferably patient name, PHN, and date of birth and ship to the address below. Samples should be shipped at room temperature with a completed MGL Requisition to arrive Monday to Friday (not on Canadian statutory holidays). 

Prenatal Specimens
Prenatal testing REQUIRES LABORATORY CONSULTATION PRIOR TO THE PROCEDURE and can only be ordered by a Medical Geneticist. Contact the laboratory at 604-875-2852 and choose the appropriate option for the Molecular Geneticist on service.
Chorionic Villi: 20 mg.
Direct Amniotic fluid: 25 mL collected in two separate tubes of equal volume.
Cultured Amniocytes: Two (2) 100% confluent T-25 flasks.

Label each sample with three patient identifiers; preferably patient name, PHN, and date of birth. Ship samples by overnight courier with a completed MGL Requisition to arrive Monday to Friday (not on Canadian statutory holidays) as follows:

• Villi – on wet ice or in media at room temperature
• Amniocytes, Amniotic fluid, DNA – at room temperature

Testing is only available to residents of Canada, except in very specific circumstances where testing is urgent or emergent.  Payment is not required when requests are made for individuals who are insured by Health Insurance BC (administered through the BC Medical Services Plan (MSP)) AND eligible for testing according to the test utilization guidelines / policy. If the individual undergoing testing is not insured by these providers or does not meet utilization guidelines or policy, please complete a billing form; testing will only commence after receipt of billing informationTest prices can be found here.

Molecular genetic testing is limited by the current understanding of the genome and the genetics of a particular disease, as well as by the method of detection used. This method will not detect all mutations (e.g., point mutations in the coding region, promoter mutations, and regulatory element mutations). In rare cases, a point mutation could be detected.

For carrier/predictive testing due to family history, it is generally important to first document the gene mutation in an affected or carrier family member. This information should be provided to the laboratory for assessment of whether the assay is appropriate for detection of the familial mutation, and to aid in the interpretation of data.

In some cases, DNA alterations of undetermined or unclear clinical significance may be identified.

Rare single nucleotide variants or polymorphisms could lead to false-negative results. If results obtained do not match the clinical findings, consult the on-service Molecular Geneticist.

A previous bone marrow transplant from an allogenic donor will result in molecular data that reflects the donor genotype rather than the recipient (patient) genotype. Consult the on-service Molecular Geneticist for approach to testing in such individuals.

Transfusions performed with packed red blood cells will generally not affect the outcome of molecular genetic testing. However, if there is no clinical urgency, the cautious approach is to wait one week post packed red cell transfusion before collecting a sample for genetic testing. Consult the on-service Molecular Geneticist as needed.

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.

Proximal Myotonic Myopathy (PROMM); Ricker Syndrome; DM2

Myotonic Dystrophy Type 2 (DM2) is characterized by myotonia and muscle dysfunction (weakness, pain and stiffness), and may include other multi-system involvement including cataracts and type 2 diabetes.  Onset of symptoms usually occurs between the second to seventh decade, most typically in the third or fourth decade. See PMID: 20301639 for an overview.

DM2 is an autosomal dominant disorder caused by expansion of a CCTG repeat in intron 1 of the CNBP gene.  The CCTG repeat is part of a complex repeat motif consisting of (TG)_n(TCTG)_n(CCTG)_n.

CNBP alleles are typically classified based on total size of the repeat motif, which roughly translates to:

• Normal alleles: up to ~54 CCTG repeats, including mutable normal alleles (27 – ~54 CCTG repeats)
• Full Penetrance: ~55 to over 11,000 CCTG repeats, with a mean of 5000 repeats.

There is no known correlation between the size of the expansion and the severity of the symptoms.

CCTG repeat alleles in the mutable normal range are rare and, as such, their clinical significance is not well characterized.

1. Confirmation of diagnosis:
   1. In individuals with clinical features suggestive of myotonic dystrophy.
2. Presymptomatic testing:
   1. In adults known to be at risk of myotonic dystrophy type 2 because of a molecularly confirmed family history of the condition.

Standard PCR amplification is performed across the (TG)_n(TCTG)_n(CCTG)_n repeat tract of the CNBP gene.  Repeat-primed PCR amplification is performed to assess for the presence of expanded allele(s) not amplifiable by standard PCR.  Repeat size, beyond normal or expanded, is not reported.

Blood: 4 mL EDTA is optimal (Minimum: 1 mL EDTA)
DNA: 100 μL at 200 ng/μL is optimal (Minimum: 30 μL at 200 ng/μL)

Label each sample with three patient identifiers; preferably patient name, PHN, and date of birth and ship to the address below. Samples should be shipped at room temperature with a completed MGL Requisition to arrive Monday to Friday (not on Canadian statutory holidays).  

Shipping Address

Testing is only available to residents of Canada, except in very specific circumstances where testing is urgent or emergent.  Payment is not required when requests are made for individuals who are insured by Health Insurance BC (administered through the BC Medical Services Plan (MSP)) AND eligible for testing according to the test utilization guidelines / policy. If the individual undergoing testing is not insured by these providers or does not meet utilization guidelines or policy, please complete a billing form; testing will only commence after receipt of billing informationTest prices can be found here.

For carrier/predictive testing due to family history, it is generally important to first document the gene mutation in an affected or carrier family member.  Ideally, this information should be provided to the laboratory for assessment of whether the assay is appropriate for detection of the familial mutation, and to aid in the interpretation of data.

In certain scenarios of repeat size mosaicism, false negative results may occur.  If results obtained do not match the clinical findings, consult the on-service Molecular Geneticist.

Rare single nucleotide variants or polymorphisms could lead to false-negative results. If results obtained do not match the clinical findings, consult the on-service Molecular Geneticist.

A previous bone marrow transplant from an allogenic donor will result in molecular data that reflects the donor genotype rather than the recipient (patient) genotype.  Consult the on-service Molecular Geneticist for approach to testing in such individuals. 

Transfusions performed with packed red blood cells will generally not affect the outcome of molecular genetic testing.  However, if there is no clinical urgency, the cautious approach is to wait one week post-packed red cell transfusion before collecting a sample for genetic testing.  Consult the on-service Molecular Geneticist as needed.

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.

Cystic fibrosis (CF) classically presents in infancy with clinical features that include chronic, debilitating lung infections and pancreatic insufficiency causing dietary malabsorption.

CFTR-related disorders (CFTR-RD) are defined as clinical entities associated with CFTR dysfunction that do not fulfill the diagnostic criteria for CF. This term has been ascribed to congenital bilateral absence of the vas deferens (CBAVD), recurrent pancreatitis, and disseminated bronchiectasis (PMID: 21658649). It is recommended that individuals with suspected CFTR-RD should have CFTR genetic testing performed in conjunction with sweat testing.

CF and CFTR-RD are autosomal recessive disorders caused by pathogenic variants in the CFTR gene, which encodes a chloride ion channel in epithelial cells. Over 2,000 different variants have been identified in CFTR; not all cause clinical symptoms and most are rare, with the exception of the CF-causing variant F508del which comprises approximately 70% of CF-causing alleles in individuals of Northern European ancestry.

1. Confirmation of diagnosis: The sweat chloride test is the gold standard test for confirming a diagnosis of cystic fibrosis (CF), and is recommended prior to or in conjunction with genetic testing in the investigation of a CFTR related disorder (CFTR-RD), depending on the clinical presentation.  Therefore, genetic testing should generally only be performed following or in conjunction with sweat testing except when:
   1. A sweat chloride test is not easily obtained (e.g., newborn with meconium ileus) OR
   2. A male has documented evidence of CBAVD and his partner is a known carrier of a CF-causing variant.
2. Carrier testing:
   1. Adults whose CF carrier risk due to a personal family history is greater than that of the general population OR their partner has a family history and CF carrier risk greater than that of the general population.
   2. Parents of a pregnancy where echogenic bowel has been detected on fetal ultrasound AND both of the parents are of an ancestry where the carrier frequency of CF is high and the detection rate of the assay is high (generally this applies to individuals of Northern-European ancestry or Ashkenazi Jewish ancestry).
3. Prenatal testing (prenatal diagnosis requests are not normally accepted from physicians other than Medical Geneticists):
   1. Pregnancies known to be at risk of CF AND the CF-causing variants segregating in the parents are known. 
4. Newborn screening:
   1. As part of the BC Newborn Screening Program, infants with an elevated immunoreactive trypsinogen (IRT) will undergo CFTR molecular genetic testing. These results are incorporated into the patient’s newborn screening report.

1. Population-based carrier screening for the purposes of reproductive planning is not covered by Health Insurance BC (BC MSP).
2. Testing of individuals with infertility who do not meet clinical criteria for CFTR-related CBAVD is not covered by Health Insurance BC (BC MSP)

One hundred and thirty (130) variants classified as CF-causing by the CFTR2 project are assessed using the MiSeqDx Cystic Fibrosis 139-Variant Assay (Illumina, Inc).   The length of the poly-T tract of intron 8 is reported according to published guidelines.  

The list of variants and the associated quality metrics are available here. 

If the clinical suspicion of CF is high, and two CF-causing variants are not identified by the targeted 130 variant assay, an expanded panel of variants or full gene sequencing may be performed; the clinical report methodology will indicate the analysis performed.

The list of expanded panel variants and the associated quality metrics are available here.

The target regions covered by full gene sequencing and the associated assay quality metrics are available here.

Pregnancy-related/Prenatal

3 weeks

Blood: 4 mL EDTA is optimal (Minimum: 1 mL EDTA)
DNA: 100 μL at 200 ng/μL is optimal (Minimum: 30 μL at 200 ng/μL)

Label each sample with three patient identifiers; preferably patient name, PHN, and date of birth and ship to the address below. Samples should be shipped at room temperature with a completed MGL Requisition to arrive Monday to Friday (not on Canadian statutory holidays).  

Prenatal Specimens
Prenatal testing REQUIRES LABORATORY CONSULTATION PRIOR TO THE PROCEDURE and can only be ordered by a Medical Geneticist. Contact the laboratory at 604-875-2852 and choose the appropriate option for the Molecular Geneticist on service.
Chorionic Villi: 20 mg.
Direct Amniotic fluid: 25 mL collected in two separate tubes of equal volume.
Cultured Amniocytes: Two (2) 100% confluent T-25 flasks.
DNA extracted from prenatal specimens: 100 μL at 200 ng/μL is optimal (Minimum: 30 μL at 200 ng/μL)

Label each sample with three patient identifiers; preferably patient name, PHN, and date of birth. Ship samples by overnight courier with a completed MGL Requisition to arrive Monday to Friday (not on Canadian statutory holidays) as follows:

• Villi – on wet ice or in media at room temperature
• Amniocytes, Amniotic fluid, DNA – at room temperature

Testing is only available to residents of Canada, except in very specific circumstances where testing is urgent or emergent.  Payment is not required when requests are made for individuals who are insured by Health Insurance BC (administered through the BC Medical Services Plan (MSP)) AND eligible for testing according to the test utilization guidelines / policy. If the individual undergoing testing is not insured by these providers or does not meet utilization guidelines or policy, please complete a billing form; testing will only commence after receipt of billing informationTest prices can be found here.

Molecular genetic testing is limited by the current understanding of the genome and the genetics of a particular disease, as well as by the method of detection used.

Rare single nucleotide variants or polymorphisms could lead to false-negative or false-positive results.  Some genetic abnormalities may not be detected by this assay including: some insertions and deletions, copy number variants, and chromosomal rearrangements.  This test cannot reliably detect mosaicism.  If results obtained do not match the clinical findings, consult the on-service Molecular Geneticist

A previous bone marrow transplant from an allogenic donor will result in molecular data that reflects the donor genotype rather than the recipient (patient) genotype. Consult the on-service Molecular Geneticist for approach to testing in such individuals.

Transfusions performed with packed red blood cells will generally not affect the outcome of molecular genetic testing. However, if there is no clinical urgency, the cautious approach is to wait one week post packed red cell transfusion before collecting a sample for genetic testing. Consult the on-service Molecular Geneticist as needed.

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.

Hypokalemic periodic paralysis manifests in a paralytic form (reversible, flaccid paralysis characteristically triggered by a carbohydrate-rich meal or post-exercise rest) and a myopathic form (exercise intolerance due to progressive muscle weakness). The myopathy is independent of paralytic symptoms and may be the sole manifestation of the condition.

CACNA1S and SCN4A are the only two genes known to be associated with hypokalemic periodic paralysis (HypoPP).  Inheritance is autosomal dominant and most affected individuals will have an affected parent.  This assay will detect recurrent variants in CACNA1S exons 11 and 30 (including c.1583G>A (p.Arg528His), c.1582C>G (p.Arg528Gly), c.3716G>A (p.Arg1239His), c.3715C>G (p.Arg1239Gly) and c.1466G>A (p.Arg489His)) accounting for approximately 43-67% of cases, and recurrent variants in SCN4A exon 12 (including c.2005C>G (p.Arg669Gly), c.2006G>A (p.Arg669His), c.2014C>A (p.Arg672Ser), c.2015G>A (p.Arg672His), c.2014C>G (p.Arg672Gly), c.2014C>T (p.Arg672Cys)) accounting for an additional 4-15% of cases.  Around one third of individuals with HypoPP will have no variants identified.

1. Confirmation of diagnosis:
   1. In individuals with clinical features suggestive of hypokalemic periodic paralysis.
2. Prenatal testing (technically feasible but not routinely performed – contact MGL to discuss):
   1. Pregnancies known to be at risk of hypokalemic periodic paralysis when the CACNA1S or SCN4A mutation is known.
3. Presymptomatic testing:
   1. Asymptomatic children and adults at risk of this condition because of a family history. The CACNA1S or SCN4A mutation must be known.

Bidirectional Sanger sequencing of CACNA1S exons 11 and 30 and of SCN4A exon 12, and their flanking intronic sequences. These exons encompass the recurrent mutations described for this disorder.

CACNA1S: NM_000069. The ‘A’ within the initiation codon, ATG, is designated as nucleotide number 1.

SCN4A: NM_000334.4. The ‘A’ within the initiation codon, ATG, is designated as nucleotide number 1.

Blood: 4 mL EDTA is optimal (Minimum: 1 mL EDTA)
DNA: 100 μL at 200 ng/μL is optimal (Minimum: 30 μL at 200 ng/μL)

Label each sample with three patient identifiers; preferably patient name, PHN, and date of birth and ship to the address below. Samples should be shipped at room temperature with a completed MGL Requisition to arrive Monday to Friday (not on Canadian statutory holidays). 

Testing is only available to residents of Canada, except in very specific circumstances where testing is urgent or emergent.  Payment is not required when requests are made for individuals who are insured by Health Insurance BC (administered through the BC Medical Services Plan (MSP)) AND eligible for testing according to the test utilization guidelines / policy. If the individual undergoing testing is not insured by these providers or does not meet utilization guidelines or policy, please complete a billing form; testing will only commence after receipt of billing informationTest prices can be found here.

Molecular genetic testing is limited by the current understanding of the genome and the genetics of a particular disease, as well as by the method of detection used. This method will not detect all mutations (e.g., mutations outside the regions tested as described above, large genomic deletions, promoter mutations, regulatory element mutations).

For carrier/predictive testing due to family history, it is generally important to first document the gene mutation in an affected or carrier family member. This information should be provided to the laboratory for assessment of whether the assay is appropriate for detection of the familial mutation, and to aid in the interpretation of data.

In rare cases, DNA alterations of undetermined or unclear clinical significance may be identified.

Rare single nucleotide variants or polymorphisms could lead to false-negative results. If results obtained do not match the clinical findings, consult the on-service Molecular Geneticist.

A previous bone marrow transplant from an allogenic donor will result in molecular data that reflects the donor genotype rather than the recipient (patient) genotype. Consult the on-service Molecular Geneticist for approach to testing in such individuals.

Transfusions performed with packed red blood cells will generally not affect the outcome of molecular genetic testing. However, if there is no clinical urgency, the cautious approach is to wait one week post packed red cell transfusion before collecting a sample for genetic testing. Consult the on-service Molecular Geneticist as needed.

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.

Machado-Joseph Disease; Olivopontocerebellar Atrophy (OPCA); Cerebelloparenchymal Disease; Menzel type OPCA; Schut-Haymaker type OPCA; Holguin Ataxia; Wadia-Swami Syndrome; Azorean Ataxia; Spinopontine Atrophy; Nigrospinodentatal Degeneration

The spinocerebellar ataxias (SCA) are characterized by slowly progressive gait ataxia, and are often associated with poor coordination of hands, speech, and eye movement.

SCA type 1, 2, 3, 6, and 7 are autosomal dominant conditions caused by expansion of the CAG repeat in ATXN1, ATXN2, ATXN3, CACNA1A, and ATXN7 respectively. 

SCA alleles are classified based on size, and reported based on classification, as outlined below.  Exact repeat sizes are not reported:

SCA1 (ATXN1):

• Normal: ≤38 repeats or 39-44 interrupted repeats
• Full Penetrance (pathogenic): 39-44 uninterrupted repeats or ≥45 repeats

SCA2 (ATXN2)

• Normal: ≤31 repeats
• Uncertain: 32-34 repeats
• Full Penetrance (pathogenic): ≥35 repeats

SCA3 (ATXN3)

• Normal: ≤44 repeats
• Uncertain: 45-~59 repeats*
• Full Penetrance (pathogenic): ≥~60 repeats*

           *The repeat size of the smallest full penetrance pathogenic allele is not well-defined.

SCA6 (CACNA1A)

• Normal: ≤18 repeats
• Uncertain: 19 repeats
• Full Penetrance (pathogenic): ≥20 repeats

SCA7 (ATXN7)

• Normal: ≤33 repeats
• Uncertain: 34-36 repeats
• Full Penetrance (pathogenic): ≥37 repeats

1. Confirmation of diagnosis:
   1. In individuals with clinical features suggestive of SCA1, 2, 3, 6 or 7.
2. Prenatal testing (prenatal diagnosis requests are not normally accepted from physicians other than Medical Geneticists; technically feasible, but not routinely performed – contact MGL to discuss):
   1. Pregnancies at risk of being affected with one of these ataxias
3. Presymptomatic testing:
   1. Adults at risk to develop one of these ataxias due to a molecularly confirmed family history. Predictive testing will only be performed following genetic counselling by a recognized genetic service.

Sizing of the CAG repeats associated with each gene is carried out on an ABI genetic analyzer following fluorescence-based PCR amplification.  Digestion with SfaN1 is performed on SCA1 alleles between 39 – 44 repeats to differentiate between interrupted (normal) and uninterrupted (pathogenic) repeats.  Alleles ≤44 CAG repeats that are interrupted by CAT repeats are normal, whereas alleles with 39-44 uninterrupted CAG repeats are considered fully penetrant (pathogenic).  As required, triplet-primed (tp) PCR is performed for SCA2 and SCA7.

Blood: 4 mL EDTA is optimal (Minimum: 1 mL EDTA)
DNA: 100 μL at 200 ng/μL is optimal (Minimum: 30 μL at 200 ng/μL)

Label each sample with three patient identifiers; preferably patient name, PHN, and date of birth and ship to the address below. Samples should be shipped at room temperature with a completed MGL Requisition to arrive Monday to Friday (not on Canadian statutory holidays). 

Testing is only available to residents of Canada, except in very specific circumstances where testing is urgent or emergent.  Payment is not required when requests are made for individuals who are insured by Health Insurance BC (administered through the BC Medical Services Plan (MSP)) AND eligible for testing according to the test utilization guidelines / policy. If the individual undergoing testing is not insured by these providers or does not meet utilization guidelines or policy, please complete a billing form; testing will only commence after receipt of billing informationTest prices can be found here.

Molecular genetic testing is limited by the current understanding of the genome and the genetics of a particular disease, as well as by the method of detection used. This method will not detect all mutations (e.g., point mutations in the coding region of the gene, large genomic deletions, promoter mutations, regulatory element mutations). For some trinucleotide repeat disorders, repeat expansions have been described that cannot be amplified by PCR. Consideration should be given to this particularly in cases with severe clinical features or early onset; consult the on-service Molecular Geneticist to discuss specific repeat disorders.

For carrier/predictive testing due to family history, it is generally important to first document the gene mutation in an affected or carrier family member. This information should be provided to the laboratory for assessment of whether the assay is appropriate for detection of the familial mutation, and to aid in the interpretation of data.

In some cases, DNA alterations of undetermined or unclear clinical significance may be identified.

In certain scenarios of repeat size mosaicism, false negative results may occur. If results obtained do not match the clinical findings, consult the on-service Molecular Geneticist.

Rare single nucleotide variants or polymorphisms could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, consult the on-service Molecular Geneticist.

A previous bone marrow transplant from an allogenic donor will result in molecular data that reflects the donor genotype rather than the recipient (patient) genotype. Consult the on-service Molecular Geneticist for approach to testing in such individuals.

Transfusions performed with packed red blood cells will generally not affect the outcome of molecular genetic testing. However, if there is no clinical urgency, the cautious approach is to wait one week post packed red cell transfusion before collecting a sample for genetic testing. Consult the on-service Molecular Geneticist as needed.

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.

Machado-Joseph Disease; Olivopontocerebellar Atrophy (OPCA); Cerebelloparenchymal Disease; Menzel type OPCA; Schut-Haymaker type OPCA; Holguin Ataxia; Wadia-Swami Syndrome; Azorean Ataxia; Spinopontine Atrophy; Nigrospinodentatal Degeneration

The spinocerebellar ataxias (SCA) are characterized by slowly progressive gait ataxia, and are often associated with poor coordination of hands, speech, and eye movement.

SCA type 1, 2, 3, 6, and 7 are autosomal dominant conditions caused by expansion of the CAG repeat in ATXN1, ATXN2, ATXN3, CACNA1A, and ATXN7 respectively. 

SCA alleles are classified based on size, and reported based on classification, as outlined below.  Exact repeat sizes are not reported:

SCA1 (ATXN1):

• Normal: ≤38 repeats or 39-44 interrupted repeats
• Full Penetrance (pathogenic): 39-44 uninterrupted repeats or ≥45 repeats

SCA2 (ATXN2)

• Normal: ≤31 repeats
• Uncertain: 32-34 repeats
• Full Penetrance (pathogenic): ≥35 repeats

SCA3 (ATXN3)

• Normal: ≤44 repeats
• Uncertain: 45-~59 repeats*
• Full Penetrance (pathogenic): ≥~60 repeats*

           *The repeat size of the smallest full penetrance pathogenic allele is not well-defined.

SCA6 (CACNA1A)

• Normal: ≤18 repeats
• Uncertain: 19 repeats
• Full Penetrance (pathogenic): ≥20 repeats

SCA7 (ATXN7)

• Normal: ≤33 repeats
• Uncertain: 34-36 repeats
• Full Penetrance (pathogenic): ≥37 repeats

1. Confirmation of diagnosis:
   1. In individuals with clinical features suggestive of SCA1, 2, 3, 6 or 7.
2. Prenatal testing (prenatal diagnosis requests are not normally accepted from physicians other than Medical Geneticists; technically feasible, but not routinely performed – contact MGL to discuss):
   1. Pregnancies at risk of being affected with one of these ataxias
3. Presymptomatic testing:
   1. Adults at risk to develop one of these ataxias due to a molecularly confirmed family history. Predictive testing will only be performed following genetic counselling by a recognized genetic service.

Sizing of the CAG repeats associated with each gene is carried out on an ABI genetic analyzer following fluorescence-based PCR amplification.  Digestion with SfaN1 is performed on SCA1 alleles between 39 – 44 repeats to differentiate between interrupted (normal) and uninterrupted (pathogenic) repeats.  Alleles ≤44 CAG repeats that are interrupted by CAT repeats are normal, whereas alleles with 39-44 uninterrupted CAG repeats are considered fully penetrant (pathogenic).  As required, triplet-primed (tp) PCR is performed for SCA2 and SCA7.

Blood: 4 mL EDTA is optimal (Minimum: 1 mL EDTA)
DNA: 100 μL at 200 ng/μL is optimal (Minimum: 30 μL at 200 ng/μL)

Label each sample with three patient identifiers; preferably patient name, PHN, and date of birth and ship to the address below. Samples should be shipped at room temperature with a completed MGL Requisition to arrive Monday to Friday (not on Canadian statutory holidays). 

Testing is only available to residents of Canada, except in very specific circumstances where testing is urgent or emergent.  Payment is not required when requests are made for individuals who are insured by Health Insurance BC (administered through the BC Medical Services Plan (MSP)) AND eligible for testing according to the test utilization guidelines / policy. If the individual undergoing testing is not insured by these providers or does not meet utilization guidelines or policy, please complete a billing form; testing will only commence after receipt of billing informationTest prices can be found here.

Molecular genetic testing is limited by the current understanding of the genome and the genetics of a particular disease, as well as by the method of detection used. This method will not detect all mutations (e.g., point mutations in the coding region of the gene, large genomic deletions, promoter mutations, regulatory element mutations). For some trinucleotide repeat disorders, repeat expansions have been described that cannot be amplified by PCR. Consideration should be given to this particularly in cases with severe clinical features or early onset; consult the on-service Molecular Geneticist to discuss specific repeat disorders.

For carrier/predictive testing due to family history, it is generally important to first document the gene mutation in an affected or carrier family member. This information should be provided to the laboratory for assessment of whether the assay is appropriate for detection of the familial mutation, and to aid in the interpretation of data.

In some cases, DNA alterations of undetermined or unclear clinical significance may be identified.

In certain scenarios of repeat size mosaicism, false negative results may occur. If results obtained do not match the clinical findings, consult the on-service Molecular Geneticist.

Rare single nucleotide variants or polymorphisms could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, consult the on-service Molecular Geneticist.

A previous bone marrow transplant from an allogenic donor will result in molecular data that reflects the donor genotype rather than the recipient (patient) genotype. Consult the on-service Molecular Geneticist for approach to testing in such individuals.

Transfusions performed with packed red blood cells will generally not affect the outcome of molecular genetic testing. However, if there is no clinical urgency, the cautious approach is to wait one week post packed red cell transfusion before collecting a sample for genetic testing. Consult the on-service Molecular Geneticist as needed.

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.

Machado-Joseph Disease; Olivopontocerebellar Atrophy (OPCA); Cerebelloparenchymal Disease; Menzel type OPCA; Schut-Haymaker type OPCA; Holguin Ataxia; Wadia-Swami Syndrome; Azorean Ataxia; Spinopontine Atrophy; Nigrospinodentatal Degeneration

The spinocerebellar ataxias (SCA) are characterized by slowly progressive gait ataxia, and are often associated with poor coordination of hands, speech, and eye movement.

SCA type 1, 2, 3, 6, and 7 are autosomal dominant conditions caused by expansion of the CAG repeat in ATXN1, ATXN2, ATXN3, CACNA1A, and ATXN7 respectively. 

SCA alleles are classified based on size, and reported based on classification, as outlined below.  Exact repeat sizes are not reported:

SCA1 (ATXN1):

• Normal: ≤38 repeats or 39-44 interrupted repeats
• Full Penetrance (pathogenic): 39-44 uninterrupted repeats or ≥45 repeats

SCA2 (ATXN2)

• Normal: ≤31 repeats
• Uncertain: 32-34 repeats
• Full Penetrance (pathogenic): ≥35 repeats

SCA3 (ATXN3)

• Normal: ≤44 repeats
• Uncertain: 45-~59 repeats*
• Full Penetrance (pathogenic): ≥~60 repeats*

           *The repeat size of the smallest full penetrance pathogenic allele is not well-defined.

SCA6 (CACNA1A)

• Normal: ≤18 repeats
• Uncertain: 19 repeats
• Full Penetrance (pathogenic): ≥20 repeats

SCA7 (ATXN7)

• Normal: ≤33 repeats
• Uncertain: 34-36 repeats
• Full Penetrance (pathogenic): ≥37 repeats

1. Confirmation of diagnosis:
   1. In individuals with clinical features suggestive of SCA1, 2, 3, 6 or 7.
2. Prenatal testing (prenatal diagnosis requests are not normally accepted from physicians other than Medical Geneticists; technically feasible, but not routinely performed – contact MGL to discuss):
   1. Pregnancies at risk of being affected with one of these ataxias
3. Presymptomatic testing:
   1. Adults at risk to develop one of these ataxias due to a molecularly confirmed family history. Predictive testing will only be performed following genetic counselling by a recognized genetic service.

Sizing of the CAG repeats associated with each gene is carried out on an ABI genetic analyzer following fluorescence-based PCR amplification.  Digestion with SfaN1 is performed on SCA1 alleles between 39 – 44 repeats to differentiate between interrupted (normal) and uninterrupted (pathogenic) repeats.  Alleles ≤44 CAG repeats that are interrupted by CAT repeats are normal, whereas alleles with 39-44 uninterrupted CAG repeats are considered fully penetrant (pathogenic).  As required, triplet-primed (tp) PCR is performed for SCA2 and SCA7.

Blood: 4 mL EDTA is optimal (Minimum: 1 mL EDTA)
DNA: 100 μL at 200 ng/μL is optimal (Minimum: 30 μL at 200 ng/μL)

Label each sample with three patient identifiers; preferably patient name, PHN, and date of birth and ship to the address below. Samples should be shipped at room temperature with a completed MGL Requisition to arrive Monday to Friday (not on Canadian statutory holidays). 

Testing is only available to residents of Canada, except in very specific circumstances where testing is urgent or emergent.  Payment is not required when requests are made for individuals who are insured by Health Insurance BC (administered through the BC Medical Services Plan (MSP)) AND eligible for testing according to the test utilization guidelines / policy. If the individual undergoing testing is not insured by these providers or does not meet utilization guidelines or policy, please complete a billing form; testing will only commence after receipt of billing informationTest prices can be found here.

Molecular genetic testing is limited by the current understanding of the genome and the genetics of a particular disease, as well as by the method of detection used. This method will not detect all mutations (e.g., point mutations in the coding region of the gene, large genomic deletions, promoter mutations, regulatory element mutations). For some trinucleotide repeat disorders, repeat expansions have been described that cannot be amplified by PCR. Consideration should be given to this particularly in cases with severe clinical features or early onset; consult the on-service Molecular Geneticist to discuss specific repeat disorders.

For carrier/predictive testing due to family history, it is generally important to first document the gene mutation in an affected or carrier family member. This information should be provided to the laboratory for assessment of whether the assay is appropriate for detection of the familial mutation, and to aid in the interpretation of data.

In some cases, DNA alterations of undetermined or unclear clinical significance may be identified.

In certain scenarios of repeat size mosaicism, false negative results may occur. If results obtained do not match the clinical findings, consult the on-service Molecular Geneticist.

Rare single nucleotide variants or polymorphisms could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, consult the on-service Molecular Geneticist.

A previous bone marrow transplant from an allogenic donor will result in molecular data that reflects the donor genotype rather than the recipient (patient) genotype. Consult the on-service Molecular Geneticist for approach to testing in such individuals.

Transfusions performed with packed red blood cells will generally not affect the outcome of molecular genetic testing. However, if there is no clinical urgency, the cautious approach is to wait one week post packed red cell transfusion before collecting a sample for genetic testing. Consult the on-service Molecular Geneticist as needed.

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.

Machado-Joseph Disease; Olivopontocerebellar Atrophy (OPCA); Cerebelloparenchymal Disease; Menzel type OPCA; Schut-Haymaker type OPCA; Holguin Ataxia; Wadia-Swami Syndrome; Azorean Ataxia; Spinopontine Atrophy; Nigrospinodentatal Degeneration

The spinocerebellar ataxias (SCA) are characterized by slowly progressive gait ataxia, and are often associated with poor coordination of hands, speech, and eye movement.

SCA type 1, 2, 3, 6, and 7 are autosomal dominant conditions caused by expansion of the CAG repeat in ATXN1, ATXN2, ATXN3, CACNA1A, and ATXN7 respectively. 

SCA alleles are classified based on size, and reported based on classification, as outlined below.  Exact repeat sizes are not reported:

SCA1 (ATXN1):

• Normal: ≤38 repeats or 39-44 interrupted repeats
• Full Penetrance (pathogenic): 39-44 uninterrupted repeats or ≥45 repeats

SCA2 (ATXN2)

• Normal: ≤31 repeats
• Uncertain: 32-34 repeats
• Full Penetrance (pathogenic): ≥35 repeats

SCA3 (ATXN3)

• Normal: ≤44 repeats
• Uncertain: 45-~59 repeats*
• Full Penetrance (pathogenic): ≥~60 repeats*

           *The repeat size of the smallest full penetrance pathogenic allele is not well-defined.

SCA6 (CACNA1A)

• Normal: ≤18 repeats
• Uncertain: 19 repeats
• Full Penetrance (pathogenic): ≥20 repeats

SCA7 (ATXN7)

• Normal: ≤33 repeats
• Uncertain: 34-36 repeats
• Full Penetrance (pathogenic): ≥37 repeats

1. Confirmation of diagnosis:
   1. In individuals with clinical features suggestive of SCA1, 2, 3, 6 or 7.
2. Prenatal testing (prenatal diagnosis requests are not normally accepted from physicians other than Medical Geneticists; technically feasible, but not routinely performed – contact MGL to discuss):
   1. Pregnancies at risk of being affected with one of these ataxias
3. Presymptomatic testing:
   1. Adults at risk to develop one of these ataxias due to a molecularly confirmed family history. Predictive testing will only be performed following genetic counselling by a recognized genetic service.

Sizing of the CAG repeats associated with each gene is carried out on an ABI genetic analyzer following fluorescence-based PCR amplification.  Digestion with SfaN1 is performed on SCA1 alleles between 39 – 44 repeats to differentiate between interrupted (normal) and uninterrupted (pathogenic) repeats.  Alleles ≤44 CAG repeats that are interrupted by CAT repeats are normal, whereas alleles with 39-44 uninterrupted CAG repeats are considered fully penetrant (pathogenic).  As required, triplet-primed (tp) PCR is performed for SCA2 and SCA7.

Blood: 4 mL EDTA is optimal (Minimum: 1 mL EDTA)
DNA: 100 μL at 200 ng/μL is optimal (Minimum: 30 μL at 200 ng/μL)

Label each sample with three patient identifiers; preferably patient name, PHN, and date of birth and ship to the address below. Samples should be shipped at room temperature with a completed MGL Requisition to arrive Monday to Friday (not on Canadian statutory holidays). 

Testing is only available to residents of Canada, except in very specific circumstances where testing is urgent or emergent.  Payment is not required when requests are made for individuals who are insured by Health Insurance BC (administered through the BC Medical Services Plan (MSP)) AND eligible for testing according to the test utilization guidelines / policy. If the individual undergoing testing is not insured by these providers or does not meet utilization guidelines or policy, please complete a billing form; testing will only commence after receipt of billing informationTest prices can be found here.

Molecular genetic testing is limited by the current understanding of the genome and the genetics of a particular disease, as well as by the method of detection used. This method will not detect all mutations (e.g., point mutations in the coding region of the gene, large genomic deletions, promoter mutations, regulatory element mutations). For some trinucleotide repeat disorders, repeat expansions have been described that cannot be amplified by PCR. Consideration should be given to this particularly in cases with severe clinical features or early onset; consult the on-service Molecular Geneticist to discuss specific repeat disorders.

For carrier/predictive testing due to family history, it is generally important to first document the gene mutation in an affected or carrier family member. This information should be provided to the laboratory for assessment of whether the assay is appropriate for detection of the familial mutation, and to aid in the interpretation of data.

In some cases, DNA alterations of undetermined or unclear clinical significance may be identified.

In certain scenarios of repeat size mosaicism, false negative results may occur. If results obtained do not match the clinical findings, consult the on-service Molecular Geneticist.

Rare single nucleotide variants or polymorphisms could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, consult the on-service Molecular Geneticist.

A previous bone marrow transplant from an allogenic donor will result in molecular data that reflects the donor genotype rather than the recipient (patient) genotype. Consult the on-service Molecular Geneticist for approach to testing in such individuals.

Transfusions performed with packed red blood cells will generally not affect the outcome of molecular genetic testing. However, if there is no clinical urgency, the cautious approach is to wait one week post packed red cell transfusion before collecting a sample for genetic testing. Consult the on-service Molecular Geneticist as needed.

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.

Machado-Joseph Disease; Olivopontocerebellar Atrophy (OPCA); Cerebelloparenchymal Disease; Menzel type OPCA; Schut-Haymaker type OPCA; Holguin Ataxia; Wadia-Swami Syndrome; Azorean Ataxia; Spinopontine Atrophy; Nigrospinodentatal Degeneration

The spinocerebellar ataxias (SCA) are characterized by slowly progressive gait ataxia, and are often associated with poor coordination of hands, speech, and eye movement.

SCA type 1, 2, 3, 6, and 7 are autosomal dominant conditions caused by expansion of the CAG repeat in ATXN1, ATXN2, ATXN3, CACNA1A, and ATXN7 respectively. 

SCA alleles are classified based on size, and reported based on classification, as outlined below.  Exact repeat sizes are not reported:

SCA1 (ATXN1):

• Normal: ≤38 repeats or 39-44 interrupted repeats
• Full Penetrance (pathogenic): 39-44 uninterrupted repeats or ≥45 repeats

SCA2 (ATXN2)

• Normal: ≤31 repeats
• Uncertain: 32-34 repeats
• Full Penetrance (pathogenic): ≥35 repeats

SCA3 (ATXN3)

• Normal: ≤44 repeats
• Uncertain: 45-~59 repeats*
• Full Penetrance (pathogenic): ≥~60 repeats*

           *The repeat size of the smallest full penetrance pathogenic allele is not well-defined.

SCA6 (CACNA1A)

• Normal: ≤18 repeats
• Uncertain: 19 repeats
• Full Penetrance (pathogenic): ≥20 repeats

SCA7 (ATXN7)

• Normal: ≤33 repeats
• Uncertain: 34-36 repeats
• Full Penetrance (pathogenic): ≥37 repeats

1. Confirmation of diagnosis:
   1. In individuals with clinical features suggestive of SCA1, 2, 3, 6 or 7.
2. Prenatal testing (prenatal diagnosis requests are not normally accepted from physicians other than Medical Geneticists; technically feasible, but not routinely performed – contact MGL to discuss):
   1. Pregnancies at risk of being affected with one of these ataxias
3. Presymptomatic testing:
   1. Adults at risk to develop one of these ataxias due to a molecularly confirmed family history. Predictive testing will only be performed following genetic counselling by a recognized genetic service.

Sizing of the CAG repeats associated with each gene is carried out on an ABI genetic analyzer following fluorescence-based PCR amplification.  Digestion with SfaN1 is performed on SCA1 alleles between 39 – 44 repeats to differentiate between interrupted (normal) and uninterrupted (pathogenic) repeats.  Alleles ≤44 CAG repeats that are interrupted by CAT repeats are normal, whereas alleles with 39-44 uninterrupted CAG repeats are considered fully penetrant (pathogenic).  As required, triplet-primed (tp) PCR is performed for SCA2 and SCA7.

Blood: 4 mL EDTA is optimal (Minimum: 1 mL EDTA)
DNA: 100 μL at 200 ng/μL is optimal (Minimum: 30 μL at 200 ng/μL)

Label each sample with three patient identifiers; preferably patient name, PHN, and date of birth and ship to the address below. Samples should be shipped at room temperature with a completed MGL Requisition to arrive Monday to Friday (not on Canadian statutory holidays). 

Testing is only available to residents of Canada, except in very specific circumstances where testing is urgent or emergent.  Payment is not required when requests are made for individuals who are insured by Health Insurance BC (administered through the BC Medical Services Plan (MSP)) AND eligible for testing according to the test utilization guidelines / policy. If the individual undergoing testing is not insured by these providers or does not meet utilization guidelines or policy, please complete a billing form; testing will only commence after receipt of billing informationTest prices can be found here.

Molecular genetic testing is limited by the current understanding of the genome and the genetics of a particular disease, as well as by the method of detection used. This method will not detect all mutations (e.g., point mutations in the coding region of the gene, large genomic deletions, promoter mutations, regulatory element mutations). For some trinucleotide repeat disorders, repeat expansions have been described that cannot be amplified by PCR. Consideration should be given to this particularly in cases with severe clinical features or early onset; consult the on-service Molecular Geneticist to discuss specific repeat disorders.

For carrier/predictive testing due to family history, it is generally important to first document the gene mutation in an affected or carrier family member. This information should be provided to the laboratory for assessment of whether the assay is appropriate for detection of the familial mutation, and to aid in the interpretation of data.

In some cases, DNA alterations of undetermined or unclear clinical significance may be identified.

In certain scenarios of repeat size mosaicism, false negative results may occur. If results obtained do not match the clinical findings, consult the on-service Molecular Geneticist.

Rare single nucleotide variants or polymorphisms could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, consult the on-service Molecular Geneticist.

A previous bone marrow transplant from an allogenic donor will result in molecular data that reflects the donor genotype rather than the recipient (patient) genotype. Consult the on-service Molecular Geneticist for approach to testing in such individuals.

Transfusions performed with packed red blood cells will generally not affect the outcome of molecular genetic testing. However, if there is no clinical urgency, the cautious approach is to wait one week post packed red cell transfusion before collecting a sample for genetic testing. Consult the on-service Molecular Geneticist as needed.

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.