title: Novel mutation of Endothelin-B receptor gene in Waardenburg-Hirschsprung disease.
abstract: Homozygous mutations of EDNRB in human have been reported to result in Waardenburg-Hirschsprung disease (WS4), while mutated heterozygotes manifested isolated Hirschsprung disease in lower penetrance. We investigated a case of WS4 together with all members of her nuclear family for the alteration of the EDNRB gene by using PCR-SSCP and direct sequencing technique. The index patient, who was born to a family with no history of Hirschsprung disease, presented total colonic aganglionosis with small bowel extension, sensorineural hearing loss and generalized cutaneous pigmentary defects. Interestingly, both irides were normally black. The study detected a homozygous missense mutation at codon 196 in exon 2 (Ser196Asn), which has not been reported. Both parents and four in six siblings harbored heterozygous mutation without any clinical manifestation. Our findings were consistent with previous observations that full spectrum of WS4 occurred to the mutate homozygotes. Moreover, the non-penetrance of heterozygotes in our pedigree, which differs from other reports, demonstrates the high pleiotropic effect of EDNRB mutations in human.
authors.affiliation: Department of Pediatric Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Surasak
authors.initials: S
authors.lastname: Sangkhathat
authors.forename: Piyawan
authors.initials: P
authors.lastname: Chiengkriwate
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kusafuka
authors.forename: Sakda
authors.initials: S
authors.lastname: Patrapinyokul
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fukuzawa
mesh_terms: D005260:Female; D006627:Hirschsprung Disease / Q000235:genetics* / Q000473:pathology; D006720:Homozygote; D006801:Humans; D007223:Infant; D020125:Mutation, Missense; D009679:Nuclear Family; D010375:Pedigree; D010641:Phenotype; D044023:Receptor, Endothelin B / Q000235:genetics*; D014849:Waardenburg Syndrome / Q000235:genetics* / Q000473:pathology
chemical_list: D044023:Receptor, Endothelin B