1. Molecular combing reveals allelic combinations in facioscapulohumeral dystrophy
- Author
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Aaron Bensimon, Catherine Vovan, Anne Vannier, Rafaëlle Bernard, Karine Nguyen, Nicolas Lévy, Emilie Renard, Shahram Attarian, Pierre Walrafen, Jean Pouget, Nathalie Dufrane, and Charlene Chaix
- Subjects
musculoskeletal diseases ,Adult ,Male ,congenital, hereditary, and neonatal diseases and abnormalities ,Adolescent ,Locus (genetics) ,Biology ,Polymerase Chain Reaction ,medicine ,Facioscapulohumeral muscular dystrophy ,Humans ,Allele ,Muscular dystrophy ,Alleles ,Genetics ,Mosaicism ,Haplotype ,Dystrophy ,Chromosome ,Sequence Analysis, DNA ,medicine.disease ,Subtelomere ,Muscular Dystrophy, Facioscapulohumeral ,Molecular Imaging ,Neurology ,Haplotypes ,Female ,Neurology (clinical) ,Chromosomes, Human, Pair 4 - Abstract
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
- Published
- 2011