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.