title: Second locus for Hirschsprung disease/Waardenburg syndrome in a large Mennonite kindred.
abstract: We have studied a large Mennonite kindred in which 20 members were affected with Hirschsprung disease (HSCR), 5 of whom had one or more manifestations of Waardenburg syndrome (WS) type II (WS2). Eleven additional relatives had signs of WS2 without HSCR. Since HSCR and WS2 each represent perturbations of neural crest migration/differentiation, this large pedigree with apparent cosegregation of HSCR and WS2 offered an opportunity to search for linkage between these loci, candidate genes, and random DNA markers, particularly in view of recent discoveries of genes for Waardenburg syndrome type I (WS1) and Hirschsprung disease (c-ret). We have examined the following possible linked markers in 69 relatives in this family: the c-ret gene (HSCR); the human PAX3 gene (HuP2) on chromosome 2q (WS1) and placental alkaline phosphatase (ALPP) on chromosome 2q (linked to WS1); argininosuccinate synthetase (ASS) on chromosome 9q, close to ABO blood groups which have shown weak linkage to WS; and the beta 1 GABA receptor gene (GABARB1) on chromosome 4q13-11, close to c-kit, deletions of which cause piebaldism. Linkage between any of these loci and HSCR/WS in this kindred was excluded, demonstrating that there is at least one further locus for HSCR other than c-ret.
authors: Department of Biochemistry and Molecular Genetics, St. Mary's Hospital Medical School, London, United Kingdom.
authors: E
authors: E
authors: Dow
authors: S
authors: S
authors: Cross
authors: D J
authors: DJ
authors: Wolgemuth
authors: S
authors: S
authors: Lyonnet
authors: L M
authors: LM
authors: Mulligan
authors: M
authors: M
authors: Mascari
authors: R
authors: R
authors: Ladda
authors: R
authors: R
authors: Williamson
mesh_terms: D002835:Christianity; D003241:Consanguinity; D005006:Ethnicity; D005260:Female; D005799:Genes, Dominant; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D006627:Hirschsprung Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D010375:Pedigree; D017422:Sequence Analysis, DNA; D014849:Waardenburg Syndrome / Q000235:genetics*