A gene for Hirschsprung disease (megacolon) in the pericentromeric region of human chromosome 10.
Hirschsprung disease (HSCR) is characterized by a congenital absence of enteric ganglia along a variable length of the intestine. Although long considered to be a multifactorial disease, we have identified linkage in a subset of five HSCR families to the pericentromeric region of chromosome 10, thereby providing monogenic inheritance in some families. A maximum two-point lod score of 3.37 (theta = 0.045) was observed between HSCR and D10S176, under an incompletely penetrant dominant model. Multipoint, affecteds-only and non-parametric analyses supported this finding and localize this gene to a region of approximately 7 centiMorgans, in close proximity to the locus for multiple endocrine neoplasia type 2 (MEN2). The co-occurrence of these two entities in some families might be attributable to shared pathogenetic origins.
Angrist
M
M
Department of Human Genetics, University of Pittsburgh, Pennsylvania 15261.
Kauffman
E
E
Slaugenhaupt
S A
SA
Matise
T C
TC
Puffenberger
E G
EG
Washington
S S
SS
Lipson
A
A
Cass
D T
DT
Reyna
T
T
Weeks
D E
DE
D000483:Alleles; D002503:Centromere; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D005190:Family; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D005838:Genotype; D006627:Hirschsprung Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D010375:Pedigree
D005819:Genetic Markers