Congenital Heart Defects in Patients with Deletions Upstream of SOX9

Marta Sanchez-Castro; Christopher T. Gordon; Florence Petit; Alexander Nord; Patrick Callier; Joris Andrieux; Patrice Guérin; Olivier Pichon; Albert David; Véronique Abadie; Damien Bonnet; Axel Visel; Len A. Pennacchio; Jeanne Amiel; Stanislas Lyonnet; Cédric Le Caignec

doi:10.1002/humu.22449

Congenital Heart Defects in Patients with Deletions Upstream of SOX9

Marta Sanchez-Castro, Christopher T. Gordon, Florence Petit, Alexander Nord, Patrick Callier, Joris Andrieux, Patrice Guérin, Olivier Pichon, Albert David, Véronique Abadie, Damien Bonnet, Axel Visel, Len A. Pennacchio, Jeanne Amiel, Stanislas Lyonnet, Cédric Le Caignec

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

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	https://doi.org/10.1002/humu.22449
State	Published - Dec 1 2013
Externally published	Yes

Keywords

CNV
Congenital heart defect
Copy number variant
Pierre robin sequence
SOX9

ASJC Scopus subject areas

Genetics
Genetics(clinical)

Access to Document

10.1002/humu.22449

Fingerprint Dive into the research topics of 'Congenital Heart Defects in Patients with Deletions Upstream of SOX9'. Together they form a unique fingerprint.

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 › peer-review

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. / Congenital Heart Defects in Patients with Deletions Upstream of SOX9. In: Human Mutation. 2013 ; Vol. 34, No. 12. pp. 1628-1631.

@article{2a3cfdb4da9f45259cdf1053fe18631d,

title = "Congenital Heart Defects in Patients with Deletions Upstream of SOX9",

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.",

keywords = "CNV, Congenital heart defect, Copy number variant, Pierre robin sequence, SOX9",

author = "Marta Sanchez-Castro and Gordon, {Christopher T.} and Florence Petit and Alexander Nord and Patrick Callier and Joris Andrieux and Patrice Gu{\'e}rin and Olivier Pichon and Albert David and V{\'e}ronique Abadie and Damien Bonnet and Axel Visel and Pennacchio, {Len A.} and Jeanne Amiel and Stanislas Lyonnet and {Le Caignec}, C{\'e}dric",

year = "2013",

month = dec,

day = "1",

doi = "10.1002/humu.22449",

language = "English (US)",

volume = "34",

pages = "1628--1631",

journal = "Human Mutation",

issn = "1059-7794",

publisher = "Wiley-Liss Inc.",

number = "12",

}

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 -