Abstract

--- - Objective Agenesis of the corpus callosum (ACC) is the most common malformation of the central nervous system and may be associated with mental retardation. ACC is found in 40% of the cases of Mowat-Wilson syndrome (MWS), a polytopic embryonic defect including a distinctive facial gestalt, severe mental retardation, epilepsy and postnatal microcephaly as constant features. Other manifestations involve Hirschsprung disease, cardiac defects, renal abnormalities and hypospadias. Among this broad spectrum of malformations recently associated with haploinsufficiency of the zinc finger homeobox 1B gene (ZFHX1B), ACC can therefore be the only feature to be detected prenatally. Thus, we studied a group of 18 fetuses terminated for ACC and performed mutational analysis of the ZFHX1B gene in six selected cases. - Methods Diagnosis of agenesis of the ACC was performed by prenatal echography survey. Screening for ZFHX1B deletions was performed by poly (CA) microsatellite markers studies and real-time semi-quantitative PCR. Mutational analysis was performed by single-strand conformation polymorphisms analysis (SSCP). - Results Neither deletion encompassing the ZFHX1B locus nor mutation could be detected in any of the six fetuses analysed. - Conclusion ZFHX1B is not a major gene in isolated ACC. However, analysis of MWS should be considered in the differential diagnosis of ACC, especially when the facial features raise the possibility of MWS. Copyright (C) 2004 John Wiley Sons, Ltd.