A GENE FOR HIRSCHSPRUNG DISEASE (MEGACOLON) IN THE PERICENTROMERIC REGION OF HUMAN CHROMOSOME-10

Hirschsprung disease (HSCR) is characterized by a congenital absence o f enteric ganglia along a variable length of the intestine. Although l ong considered to be a multifactorial disease, we have identified link age in a subset of five HSCR families to the pericentromeric region of chromosome 10, thereby proving monogenic inheritance in some families . A maximum two-point lod score of 3.37 (theta = 0.045) was observed b etween HSCR and D10S176, under an incompletely penetrant dominant mode l. Multipoint, affecteds-only and non-parametric analyses supported th is finding and localize this gene to a region of almost-equal-to 7 cen tiMorgans, in close proximity to the locus for multiple endocrine neop lasia type 2 (MEN2). The co-occurrence of these two entities in some f amilies might be attributable to shared pathogenetic origins.