Disruption of the SEMA3D Gene in a Patient with Congenital Heart Defects. Issue 1 (28th November 2014)

• Record Type: Journal Article
• Authors: Sanchez‐Castro, Marta; Pichon, Olivier; Briand, Annaig; Poulain, Damien; Gournay, Véronique; David, Albert; Caignec, Cédric Le
• Is Part Of: Human mutation. Volume 36:Issue 1(2015:Jan.)
• Page Start: 30
• Page End: 33
• Publication Date: 2014-11-28
• Subjects: Human chromosome abnormalities -- Periodicals; Mutation (Biology) -- Periodicals; 616.04205
• DOI: 10.1002/humu.22702
• Languages: English
• ISSNs: 1059-7794

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <p>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 <italic>semaphorin3D</italic> (<italic>SEMA3D)</italic>. Breakpoint sequencing and fiber fluorescent in situ hybridization showed tandem duplication. Expression studies showed a higher level of <italic>SEMA3D</italic> mRNA in patient's lymphoblasts versus controls. Moreover, we demonstrated the presence of a truncated <italic>SEMA3D</italic> poly‐A tailed mRNA, resulting from an abnormal transcription of <italic>SEMA3D</italic> partial duplication. Sema3D is an axon guidance protein essential for the correct migration of cardiac neural crest cells (CNCC) into the outflow tract. <italic>Sema3D^−/−</italic> 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.</p> </abstract>