Format

Send to

Choose Destination
See comment in PubMed Commons below
Ann Neurol. 2011 Oct;70(4):627-33. doi: 10.1002/ana.22513.

Molecular combing reveals allelic combinations in facioscapulohumeral dystrophy.

Author information

1
Assistance Publique-Hôpitaux de Marseille, Department of Medical Genetics, Timone Children's Hospital, Marseille, France.

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.

PMID:
22028222
DOI:
10.1002/ana.22513
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Wiley
    Loading ...
    Support Center