Nonsense mutations of the ZFHX1B gene in two Japanese girls with Mowat-Wilson syndrome.

Mowat-Wilson syndrome (MWS) is a multiple congenital anomaly-mental retardation complex caused by mutations in the Zinc Finger Homeobox 1 B gene (ZFHX1B). MWS has been reported in association with Hirschsprung disease (HSCR). MWS is sometimes difficult to diagnose clinically, especially when HSCR is absent. Thus, it is necessary to detect gene abnormalities at the molecular level. Here we report two Japanese girls with MWS, who showed a distinct facial phenotype, severe intellectual disability and epileptic seizures. Major congenital anomalies of the patients were very different. Patient 1 suffered from severe congenital heart disease, but did not show apparent HSCR. Patient 2 suffered from typical HSCR and underwent surgical treatment, but did not have congenital heart disease. According to the gene analysis using white blood cells, they had nonsense mutations in ZFHX1B, R695X and Q433X, respectively. In conclusion, molecular genetic analysis of ZFHX1B is important for a definite diagnosis of MWS which has a wide phenotypic spectrum of congenital anomalies.