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Congenital Heart Defects in Patients with Deletions Upstream of SOX 9
Author(s) -
SanchezCastro Marta,
Gordon Christopher T.,
Petit Florence,
Nord Alex S.,
Callier Patrick,
Andrieux Joris,
Guérin Patrice,
Pichon Olivier,
David Albert,
Abadie Véronique,
Bonnet Damien,
Visel Axel,
Pennacchio Len A.,
Amiel Jeanne,
Lyonnet Stanislas,
Le Caignec Cédric
Publication year - 2013
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22449
Subject(s) - sox9 , biology , enhancer , genetics , gata4 , transcription factor , dysplasia , gene
Heterozygous loss‐of‐function coding‐sequence mutations of the transcription factor SOX 9 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 ∼1 Mb deletion upstream of SOX 9 . 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 SOX 9 may be responsible for CHD s in humans.