Prenatal detection and mapping of a distal 8p deletion associated with congenital heart disease

We report the prenatal diagnosis, at 18 weeks' gestational age of a del(8)( p23.l --> pter) in a fetus with an atrio-ventricular canal, persistent left superior vena cava and hypoplastic right ventricle detected by sonographic imaging. We further refine the breakpoints associated with this defect usi ng fluorescent in situ hybridization analysis (FISH). Our findings correlat e with recent reports of the localization and importance of GATA4 (a zinc f inger transcription factor) in cardiac development. Though microcephaly, me ntal retardation and typical behavioural features are well described in var ious deletions in 8p, the absence of notable microcephaly in this case rais es the possibility for a separate genetic aetiology for some of these featu res. Indeed, primary autosomal recessive microcephaly (MCPH1) was recently mapped to a nearby region and may be the cause for this frequent observatio n in some cases of 8p deletions. These observations illustrate the role of FISH in prenatal diagnosis and refinement of chromosomal breakpoints. In ad dition, mappings of loci significant for cardiac development are presented. Our findings suggest that some features of the 8p deletion syndrome may ul timately be uncoupled from one another, and underscore the need for further study of this region of chromosome 8, in order to achieve adequate informa tion for genetic counselling. Copyright (C) 1999 John Wiley & Sons, Ltd.