Dystroglycan-Related Congenital Muscular Dystrophy Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10339 B3GALNT2 81479,81479 Order Options and Pricing
B4GAT1 81479,81479
CRPPA 81405,81479
DAG1 81479,81479
DPM1 81479,81479
DPM2 81479,81479
DPM3 81479,81479
FKRP 81404,81479
FKTN 81405,81479
GMPPB 81479,81479
GOSR2 81479,81479
LARGE1 81479,81479
POMGNT1 81406,81479
POMGNT2 81479,81479
POMK 81479,81479
POMT1 81406,81479
POMT2 81406,81479
RXYLT1 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10339Genes x (18)81479 81404, 81405, 81406, 81479 $890 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our PGxome Custom Panel tool.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

For Reflex to PGxome pricing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

The congenital muscular dystrophies are a clinically and genetically heterogeneous group of disorders characterized by elevated serum CpK levels, muscle weakness, a dystrophic process observed in biopsied muscle, and variable associated findings such as central nervous system abnormalities, cardiac muscle involvement, skeletal effects, and developmental delay. Onset of symptoms generally occurs at birth, although some symptoms do not manifest themselves until later in life. See Sparks et al. (2012) for diagnostic strategies and a comprehensive review of the congenital muscular dystrophies.

Pathogenic variants in a growing number of proven or putative O-linked and N-linked glycosyltransferase genes and one putative lipid biosynthesis gene (CRPPA/ISPD, Willer et al. 2012; Roscioli et al. 2012) cause muscular dystrophies in the dystroglycanopathy spectrum. Walker-Warburg syndrome (WWS), a severe congenital muscular dystrophy with defective neuronal migration and associated structural brain and eye abnormalities, is the most severe manifestation. Other presentations include muscle-eye-brain disease (MEB), Fukuyama congenital muscular dystrophy (FCMD), and congenital or limb girdle muscular dystrophy with associated cognitive impairment, but without structural brain abnormalities (eg., LGMD2K) (Godfrey et al. 2007). Dystroglycanopathy may manifest primarily as a cardiomyopathy with minimal skeletal muscle involvement (Margeta et al. 2009).

Genetics

The dystroglycanopathies are inherited in an autosomal recessive manner. Glycosyltransferase activity is necessary for proper post translational processing of alpha dystroglycan (ADG), a protein encoded by DAG1. In the absence of these proteins, ADG remains hypoglycosylated and diverse pathologies follow (Barresi and Campbell 2006). Molecular diagnosis (and classification) of the dystroglycanopathy subtypes is complex because extensive genetic heterogeneity exists for each disorder (Godfrey et al. 2007), and because the reported phenotypes caused by the glycosyltransferase genes continue to expand (van Reeuwijk et al. 2006). Evaluation of a patient’s muscle biopsy by immunofluorescence can detect abnormal glycosylation of ADG and can, therefore, aid in a diagnostic evaluation.

See individual gene test descriptions for information on molecular biology of gene products.

Clinical Sensitivity - Sequencing with CNV PGxome

Because of extensive phenotypic and locus heterogeneity for these disorders, clinical sensitivity is difficult to estimate. In one cohort of ninety fetuses with severe cobblestone lissencephaly and associated findings consistent with Walker-Warburg syndrome, Vuillaumier-Barrot et al. (2012), obtained a genetic diagnosis in 58 cases, or 64%. These diagnosed cases had relative frequencies as follows: POMT1 (42%), POMT2 (17%), POMGNT1 (17%), CRPPA/ISPD (9%), RXYLT1/TMEM5 (9%), LARGE1 (3%) and FKRP (3%).

Clinical sensitivity of deletion/duplication testing for the dystroglycanopathy genes is low. Gross copy number mutations are found at a significant frequency only in the CRPPA/ISPD and LARGE1 genes, and not the other dystroglycanopathy genes.

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel provides 100% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing.

This test includes coverage of the FKTN deep intronic Korean founder variant c.648-1243 G>T as well as c.1045-22A>G. This test will not detect the FKTN Japanese founder variant which is a 3kb retrotransposan insertion in the 3' UTR.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Elevated serum CpK at birth or early in life. Hypoglycosylation of alpha dystroglycan.

Genes

Official Gene Symbol OMIM ID
B3GALNT2 610194
B4GAT1 605517
CRPPA 614631
DAG1 128239
DPM1 603503
DPM2 603564
DPM3 605951
FKRP 606596
FKTN 607440
GMPPB 615320
GOSR2 604027
LARGE1 603590
POMGNT1 606822
POMGNT2 614828
POMK 615247
POMT1 607423
POMT2 607439
RXYLT1 605862
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Diseases

Name Inheritance OMIM ID
Congenital Disorder Of Glycosylation Type 1E AR 608799
Congenital Disorder Of Glycosylation Type 1O AR 612937
Congenital Disorder of Glycosylation Type Iu AR 615042
Congenital Muscular Dystrophy-Dystroglycanopathy (With Brain And Eye Anomalies) Type A5 AR 613153
Congenital Muscular Dystrophy-Dystroglycanopathy (With Or Without Mental Retardation) Type 5B AR 606612
Fukuyama Congenital Muscular Dystrophy AR 253800
Muscle Eye Brain Disease AR 253280
Muscular Dystrophy-Dystroglycanopathy (Congenital with Brain and Eye Anomalies), Type A, 10; MDDGA10 AR 615041
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12 AR 615249
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 13 AR 615287
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 AR 615350
Muscular Dystrophy-Dystroglycanopathy (Congenital With Brain And Eye Anomalies), Type A, 2 AR 613150
Muscular Dystrophy-Dystroglycanopathy (Congenital With Brain And Eye Anomalies), Type A, 6 AR 613154
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7 AR 614643
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 11 AR 615181
Muscular Dystrophy-Dystroglycanopathy (Congenital With Mental Retardation), Type B, 1 AR 613155
Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 14 AR 615351
Muscular Dystrophy-Dystroglycanopathy (Congenital With Mental Retardation), Type B, 2 AR 613156
Muscular Dystrophy-Dystroglycanopathy (Congenital With Mental Retardation), Type B, 3 AR 613151
Muscular Dystrophy-Dystroglycanopathy (Congenital With Mental Retardation), Type B, 6 AR 608840
Muscular Dystrophy-Dystroglycanopathy (Congenital Without Mental Retardation), Type B, 4 AR 613152
Muscular Dystrophy-Dystroglycanopathy (Limb-Girdle), Type C, 9 AR 613818
Walker-Warburg Congenital Muscular Dystrophy AR 236670

Related Test

Name
PGxome®

Citations

  • Barresi R., Campbell K.P. 2006. Journal of Cell Science. 119: 199-207. PubMed ID: 16410545
  • Godfrey C. et al. 2007. Brain. 130: 2725-35. PubMed ID: 17878207
  • Margeta M. et al. 2009. Muscle & Nerve. 40: 883-9. PubMed ID: 19705481
  • Roscioli T. et al. 2012. Nature Genetics. 44: 581-5. PubMed ID: 22522421
  • Sparks S. et al. 2012. Congenital Muscular Dystrophy Overview. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301468
  • van Reeuwijk J. et al. 2006. Human Mutation. 27: 453-9. PubMed ID: 16575835
  • Vuillaumier-Barrot S. et al. 2012. American Journal of Human Genetics. 91: 1135-43. PubMed ID: 23217329
  • Willer T. et al. 2012. Nature Genetics. 44: 575-80. PubMed ID: 22522420

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

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2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

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