Abstract
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 ∼1 Mb 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1628-1631 |
| Number of pages | 4 |
| Journal | Human Mutation |
| Volume | 34 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 1 2013 |
| Externally published | Yes |
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Keywords
- CNV
- Congenital heart defect
- Copy number variant
- Pierre robin sequence
- SOX9
ASJC Scopus subject areas
- Genetics
- Genetics(clinical)
Cite this
Congenital Heart Defects in Patients with Deletions Upstream of SOX9. / Sanchez-Castro, Marta; Gordon, Christopher T.; Petit, Florence; Nord, Alexander; 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.
In: Human Mutation, Vol. 34, No. 12, 01.12.2013, p. 1628-1631.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Congenital Heart Defects in Patients with Deletions Upstream of SOX9
AU - Sanchez-Castro, Marta
AU - Gordon, Christopher T.
AU - Petit, Florence
AU - Nord, Alexander
AU - Callier, Patrick
AU - Andrieux, Joris
AU - Guérin, Patrice
AU - Pichon, Olivier
AU - David, Albert
AU - Abadie, Véronique
AU - Bonnet, Damien
AU - Visel, Axel
AU - Pennacchio, Len A.
AU - Amiel, Jeanne
AU - Lyonnet, Stanislas
AU - Le Caignec, Cédric
PY - 2013/12/1
Y1 - 2013/12/1
N2 - 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 ∼1 Mb 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.
AB - 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 ∼1 Mb 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.
KW - CNV
KW - Congenital heart defect
KW - Copy number variant
KW - Pierre robin sequence
KW - SOX9
UR - http://www.scopus.com/inward/record.url?scp=84887607312&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84887607312&partnerID=8YFLogxK
U2 - 10.1002/humu.22449
DO - 10.1002/humu.22449
M3 - Article
C2 - 24115316
AN - SCOPUS:84887607312
VL - 34
SP - 1628
EP - 1631
JO - Human Mutation
JF - Human Mutation
SN - 1059-7794
IS - 12
ER -