Premium
Disruption of the SEMA 3 D Gene in a Patient with Congenital Heart Defects
Author(s) -
SanchezCastro Marta,
Pichon Olivier,
Briand Annaig,
Poulain Damien,
Gournay Véronique,
David Albert,
Caignec Cédric Le
Publication year - 2015
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.22702
Subject(s) - biology , heart development , gene duplication , in situ hybridization , anatomy , genetics , messenger rna , gene , embryonic stem cell
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 semaphorin3 D ( SEMA 3 D ) . Breakpoint sequencing and fiber fluorescent in situ hybridization showed tandem duplication. Expression studies showed a higher level of SEMA 3 D m RNA in patient's lymphoblasts versus controls. Moreover, we demonstrated the presence of a truncated SEMA 3 D poly‐ A tailed m RNA , resulting from an abnormal transcription of SEMA 3 D partial duplication. S ema3 D is an axon guidance protein essential for the correct migration of cardiac neural crest cells ( CNCC ) into the outflow tract. S ema3 D −/− mice present with CHD but its role in humans remains unclear. Our results suggest that truncated SEMA 3 D may have hampered the migration of CNCC during heart development, contributing to patient's CHD .