期刊
HUMAN MUTATION
卷 36, 期 7, 页码 679-683出版社
WILEY
DOI: 10.1002/humu.22792
关键词
FSHD; SMCHD1; epigenetic modifier; D4Z4; epiallele
资金
- European Community [2012-305121]
- Prinses Beatrix Spierfonds [W.OR12-20]
- Spieren voor Spieren
- NIH NIAMS [AR066248]
- NIH NCRR [UL1RR024160]
- FSHD Global Research Foundation
- Chromosome 18 Registry and Research Society
Facioscapulohumeral muscular dystrophy (FSHD) is most often associated with variegated expression in somatic cells of the normally repressed DUX4 gene within the D4Z4-repeat array. The most common form, FSHD1, is caused by a D4Z4-repeat array contraction to a size of 1-10 units (normal range 10-100 units). The less common form, FSHD2, is characterized by D4Z4 CpG hypomethylation and is most often caused by loss-of-function mutations in the structural maintenance of chromosomes hinge domain 1 (SMCHD1) gene on chromosome 18p. The chromatin modifier SMCHD1 is necessary to maintain a repressed D4Z4 chromatin state. Here, we describe two FSHD2 families with a 1.2-Mb deletion encompassing the SMCHD1 gene. Numerical aberrations of chromosome 18 are relatively common and the majority of 18p deletion syndrome (18p-) cases have, such as these FSHD2 families, only one copy of SMCHD1. Our finding therefore raises the possibility that 18p- cases are at risk of developing FSHD. To address this possibility, we combined genome-wide array analysis data with D4Z4 CpG methylation and repeat array sizes in individuals with 18p- and conclude that approximately 1:8 18p- cases might be at risk of developing FSHD. (C) 2015 Wiley Periodicals, Inc.
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