期刊
HUMAN MUTATION
卷 34, 期 12, 页码 1628-1631出版社
WILEY-BLACKWELL
DOI: 10.1002/humu.22449
关键词
congenital heart defect; pierre robin sequence; SOX9; copy number variant; CNV
资金
- PHRC Inter regional
- Societe Francaise de Cardiologie/Federation Francaise de Cardiologie
- Translational Research of Region des Pays de la Loire
- Ecole nationale superieure des mines de Nantes
- National Human Genome Research Institute [R01HG003988, U54HG006997]
- NIDCR [U01-DE020060]
- NIH/NIGMS F32 Fellowship [GM105202]
- Agence Nationale de la Recherche (EvoDevoMut)
Heterozygous loss-of-function coding-sequence mutations of the transcription factor SOX9 cause campomelic dysplasia, a rare skeletal dysplasia with congenital bowing of long bones (campomelia), hypoplastic scapulae, a missing pair of ribs, pelvic, and vertebral malformations, clubbed feet, Pierre Robin sequence (PRS), facial dysmorphia, and disorders of sex development. We report here two unrelated families that include patients with isolated PRS, isolated congenital heart defect (CHD), or both anomalies. Patients from both families carried a very similar approximate to 1Mb deletion upstream of SOX9. Analysis of ChIP-Seq from mouse cardiac tissue for H3K27ac, a marker of active regulatory elements, led us to identify several putative cardiac enhancers within the deleted region. One of these elements is known to interact with Nkx2.5 and Gata4, two transcription factors responsible for CHDs. Altogether, these data suggest that disruption of cardiac enhancers located upstream of SOX9 may be responsible for CHDs in humans. (C) 2013 Wiley Periodicals, Inc.
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