Novel RET mutations in Hirschsprung's disease patients from the diverse South African population

Hirschsprung's disease (HSCR) is a common cause of intestinal obstruction i n neonates with an incidence of one in 5000 live births. The disease occurs due to the absence of parasympathetic neuronal ganglia in the hindgut, res ulting in irregular or sustained contraction of the affected segment. DNA s amples of 40 unrelated subjects with HSCR were subjected to mutation screen ing of the RET (REarranged during Transfection) protooncogene, the major su sceptibility gene for HSCR. Five novel (V202M, E480K, IVS10-2A/G, D771N, IV S19-9C/T) and one previously described mutation (P973L) were identified. On ly two of the mutation-positive patients (from different ethnic groups) dis played total colonic aganglionosis, and both were heterozygous for mutation D771N. The potential disease-causing mutations occurred in 20% of individu als, with more males (22.5% representing seven of 31 males) affected than f emales (12.5% representing one of eight females). This study represents the first comprehensive genetic analysis of this disease in the diverse South African population.