Mowat-Wilson syndrome (MWS) is a recently delineated mental retardation 
(MR)-multiple congenital anomaly syndrome, characterized by typical facies, 
severe MR, epilepsy, and variable congenital malformations, including 
Hirschsprung disease (HSCR), genital anomalies, congenital heart disease (CHD), 
and agenesis of the corpus callosum (ACC). It is caused by de novo heterozygous 
mutations or deletions of the ZFHX1B gene located at 2q22. ZFHX1B encodes 
Smad-interacting protein-1 (SMADIP1 or SIP1), a transcriptional corepressor 
involved in the transforming growth factor-beta signaling pathway. It is a 
highly evolutionarily conserved gene, widely expressed in embryological 
development. Over 100 mutations have been described in patients with clinically 
typical MWS, who almost always have whole gene deletions or truncating mutations 
(nonsense or frameshift) of ZFHX1B, suggesting that haploinsufficiency is the 
basis of MWS pathology. No obvious genotype-phenotype correlation could be 
identified so far, but atypical phenotypes have been reported with missense or 
splice mutations in the ZFHX1B gene. In this work we describe 40 novel mutations 
and we summarize the various mutational reports published since the 
identification of the causative gene.