A GENE FOR HIRSCHSPRUNG DISEASE MAPS TO THE PROXIMAL LONG ARM OF CHROMOSOME-10

Hirschsprung disease (HSCR) is a frequent congenital disorder (1 in 5, 000 newborns) of unknown origin characterized by the absence of parasy mpathetic intrinsic ganglion cells of the hindgut. Taking advantage of a proximal deletion of chromosome 10q (del 10q11.2-q21.2) in a patien t with total colonic aganglionosis, and of a high-density genetic map of microsatellite DNA markers, we performed genetic linkage analysis i n 15 non-syndromic long-segment and short-segment HSCR families. Multi point linkage analysis indicated that the most likely location for a H SCR locus is between loci D10S208 and D10S196, suggesting that a domin ant gene for HSCR maps to 10q11.2, a region to which other neural cres t defects have been mapped.