Characterisation of deletions of the ZFHX1B region and genotype-phenotype analysis in Mowat-Wilson syndrome

In 1998, Mowat et al delineated a syndrome with Hirschsprung disease (HSCR) or severe constipation, microcephaly, mental retardation, and a distinctive facial appearance. Because two of the patients had a cytogenetically visible deletion of 2q22-q23, and all patients were sporadic cases, a contiguous gene syndrome or a dominant single gene disorder involving this locus were suggested. Two similar patients with cytogenetically balanced translocation t(2;13)(q22;q22) and t(2;11)(q22.2;q21), respectively, allowed Wakamatsu et al and Cacheux et al to narrow down the critical interval to 5 Mb and to one single gene respectively, which led both groups independently to the detection of intragenic mutations in the gene coding for Smad interacting protein-1 (formerly SIP1, now called zinc finger homeobox 1B (ZFHX1B)) in patients with so called "syndromic HSCR"