Mutation analysis of endothelin-B receptor gene in patients with Hirschsprung disease in Taiwan.
BACKGROUND
Endothelin-B receptor (EDNRB) signaling pathway is associated for Hirschsprung disease (HSCR). The aim of this study was to investigate the EDNRB gene mutation in patients with HSCR in Taiwan and correlate the genotype and phenotype.


METHODS
Using polymerase chain reaction amplification and direct sequencing, we screened for mutations in the coding regions and intron/exon boundaries of the EDNRB gene in 39 isolated HSCR cases and compared them with those in 400 control chromosomes.


RESULTS
In 3 cases, heterozygous variations in exon 1 and 2 of the EDNRB gene predicted missense mutations of the first cytosolic (M132I), second transmembrane (I157V), second exoplasmic (M173T), and third transmembrane (V185M) domains of the EDNRB protein. Three of the 4 mutations in our study have not been reported previously. For total 39 unrelated cases, the mutation rates were estimated to be 10% (3 of 30) for short-segment HSCR and 7.7% (3 of 39) for all HSCR cases.


CONCLUSIONS
We did not detect a significant genotype-phenotype correlation. In conclusion, this study identified 4 mutations within the EDNRB gene associated with HSCR. Because HSCR is a multifactorial and multigene disorder, the higher mutation rate of 10% for short-segment HSCR suggests the important role that the EDNRB gene plays in the pathogenesis of short-segment HSCR in Taiwan.
Lin
Yu-Cheng
YC
Department of Pediatrics, Far Eastern Memorial Hospital, Taiwan.
Lai
Hong-Shiee
HS
Hsu
Wen-Ming
WM
Lee
Ping-Ing
PI
Chen
Huey-Ling
HL
Chang
Mei-Hwei
MH
D004247:DNA / Q000097:blood; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006627:Hirschsprung Disease / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D044023:Receptor, Endothelin B / Q000235:genetics*; D013624:Taiwan
D044023:Receptor, Endothelin B; D004247:DNA