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 journalArticle

21 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)1628-1631
Number of pages4
JournalHuman Mutation
Volume34
Issue number12
DOIs
StatePublished - Dec 1 2013
Externally publishedYes

Fingerprint

Pierre Robin Syndrome
Congenital Heart Defects
SOX9 Transcription Factor
Campomelic Dysplasia
Disorders of Sex Development
Scapula
Ribs
Foot
Transcription Factors
Bone and Bones
Mutation

Keywords

  • CNV
  • Congenital heart defect
  • Copy number variant
  • Pierre robin sequence
  • SOX9

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Sanchez-Castro, M., Gordon, C. T., Petit, F., Nord, A., Callier, P., Andrieux, J., ... Le Caignec, C. (2013). Congenital Heart Defects in Patients with Deletions Upstream of SOX9. Human Mutation, 34(12), 1628-1631. https://doi.org/10.1002/humu.22449

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 journalArticle

Sanchez-Castro, M, Gordon, CT, Petit, F, Nord, A, Callier, P, Andrieux, J, Guérin, P, Pichon, O, David, A, Abadie, V, Bonnet, D, Visel, A, Pennacchio, LA, Amiel, J, Lyonnet, S & Le Caignec, C 2013, 'Congenital Heart Defects in Patients with Deletions Upstream of SOX9', Human Mutation, vol. 34, no. 12, pp. 1628-1631. https://doi.org/10.1002/humu.22449
Sanchez-Castro M, Gordon CT, Petit F, Nord A, Callier P, Andrieux J et al. Congenital Heart Defects in Patients with Deletions Upstream of SOX9. Human Mutation. 2013 Dec 1;34(12):1628-1631. https://doi.org/10.1002/humu.22449
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.
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