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Molecular combing reveals allelic combinations in facioscapulohumeral dystrophy
Author(s) -
Nguyen Karine,
Walrafen Pierre,
Bernard Rafaëlle,
Attarian Shahram,
Chaix Charlène,
Vovan Catherine,
Renard Emilie,
Dufrane Nathalie,
Pouget Jean,
Vannier Anne,
Bensimon Aaron,
Lévy Nicolas
Publication year - 2011
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.22513
Subject(s) - facioscapulohumeral muscular dystrophy , subtelomere , genetics , locus (genetics) , biology , muscular dystrophy , chromosome , allele , mendelian inheritance , haplotype , computational biology , gene
Objective: The genetic variation underlying facioscapulohumeral muscular dystrophy (FSHD), 1 of the most common hereditary neuromuscular disorders, is complex, and associated with the contraction of a repeat array ( D4Z4 ) at the subtelomeric end of chromosome 4q. Nonpathogenic variants of 4q and the presence of a homologous array on chromosome 10q make FSHD diagnosis extremely challenging, at least in individuals with nonstandard D4Z4 arrays. We aimed to improve FSHD molecular analysis by proposing an alternative technique to the Southern blot. Methods: We applied molecular combing (MC) to directly visualize allelic combinations associated with FSHD. Results: MC enabled the accurate diagnosis of 32 FSHD patients. Unreported haplotypes and rearrangements, as well as somatic mosaicism, which is common in the 10 to 30% of cases that are sporadic, were detectable by MC. Interpretation: MC enables the detailed exploration of the FSHD locus and accurate diagnosis of FSHD, the first Mendelian disease to benefit from this technique. MC is also likely to be applicable to other copy number‐variant or repeat expansion‐associated human diseases. ANN NEUROL 2011;70:627–633