Disruption of the SEMA3D gene in a patient with congenital heart defects - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Human Mutation Année : 2015

Disruption of the SEMA3D gene in a patient with congenital heart defects

Résumé

Congenital heart defect (CHD) is the leading malformation among newborns. However, its genetic basis remains mostly unknown. We report a child with transposition of the great arteries, ventricular septal defect, and coarctation of the aorta. By array comparative genomic hybridization, we identified a duplication of the 5' half of semaphorin3D (SEMA3D). Breakpoint sequencing and fiber fluorescent in situ hybridization showed tandem duplication. Expression studies showed a higher level of SEMA3D mRNA in patient's lymphoblasts versus controls. Moreover, we demonstrated the presence of a truncated SEMA3D poly-A tailed mRNA, resulting from an abnormal transcription of SEMA3D partial duplication. Sema3D is an axon guidance protein essential for the correct migration of cardiac neural crest cells (CNCC) into the outflow tract. Sema3D(-/-) mice present with CHD but its role in humans remains unclear. Our results suggest that truncated SEMA3D may have hampered the migration of CNCC during heart development, contributing to patient's CHD.

Dates et versions

hal-01830986 , version 1 (05-07-2018)

Identifiants

Citer

Marta Sanchez-Castro, Olivier Pichon, Annaig Briand, Damien Poulain, Véronique Gournay, et al.. Disruption of the SEMA3D gene in a patient with congenital heart defects. Human Mutation, 2015, Equipe 3, 36 (1), pp.30--33. ⟨10.1002/humu.22702⟩. ⟨hal-01830986⟩
54 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More