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Diagnostic Testing for Congenital Muscular Dystrophies in a Cohort of USA Patients
Author(s) -
Moore Steven Allen,
Lamande Shireen R.,
Winder Thomas L.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.708.21
Subject(s) - congenital muscular dystrophy , immunostaining , genetic heterogeneity , genetic testing , medicine , muscle biopsy , population , pathology , genetics , biopsy , phenotype , gene , muscular dystrophy , biology , immunohistochemistry , environmental health
The congenital muscular dystrophies (CMD) are a genetically and phenotypically heterogeneous group of neuromuscular and developmental diseases. Since the 1995 report that LAMA2 mutations are responsible for merosin‐deficient CMD, twelve additional CMD genes have now been identified. Diagnostic testing for CMD began at The University of Iowa in 1997 with an immunostaining panel of 4 antibodies that has now expanded to include 15 antibodies. Molecular genetic testing using direct DNA sequencing of the CMD genes responsible for dystroglycanopathies has been added since 2004. 147 muscle biopsies and 62 DNA samples have now been evaluated for patients with a clinical diagnosis of CMD; 33 cases had a biopsy and DNA. Immunostaining abnormalities were diagnostic in 63% of biopsies (53 dystroglycanopathy, 19 merosin‐deficient, 21 collagen VI‐deficient). Gene sequencing confirmed the diagnosis in 25 of the dystroglycanopathy patients across the clinical spectrum from WWS to MDC1C (3 POMT1 , 5 POMT2 , 1 POMGnT1 , 7 FCMD , and 9 FKRP ). Analysis of fibroblast culture collagen VI biosynthesis and cDNA has confirmed COL6 mutations in 6 patients. These data indicate that presumptive or definitive diagnoses can be made in ~70% of CMD patients. While the data suggest that dystroglycanopathies (as a group) are the most common form of CMD, a population‐based study will be needed to determine the true prevalence of CMD subtypes in the USA.