Mowat-Wilson syndrome is a genetic condition characterized by a recognizable facial phenotype in addition to moderate to severe cognitive disability with severe speech impairment and variable multiple congenital anomalies. The anomalies may include Hirschsprung disease, heart defects, structural eye anomalies including microphthalmia, agenesis of the corpus callosum, and urogenital anomalies. Microcephaly, seizure disorder and constipation are common. All typical cases result from haploinsufficiency of the ZEB2 (also known as ZFHX1B or SIP-1) gene, with over 100 distinct mutations now described. Approximately 80% of patients have a nonsense or frameshift mutation detectable by sequencing, with the rest having gross deletions necessitating a dosage sensitive assay. Here we report on the results of comprehensive molecular testing for 27 patients testing positive for MWS. Twenty-one patients had a nonsense, frameshift, or splice site mutation identified by sequencing; 14 of which localized to exon 8 and 17 of which are novel. Six patients had deletions in the ZEB2 gene, including two novel partial gene deletions. This report, the first such analysis in North American patients, adds to the growing list of both novel pathogenic mutations associated with MWS, as well as other variants in the ZEB2 gene. In addition, we suggest an economical testing strategy.
Copyright 2009 Wiley-Liss, Inc.