Mutational analysis of the endothelin-B receptor gene in Japanese Hirschsprung's disease.
OBJECTIVE
Hirschsprung's disease (HD, HSCR) is one of the most common diseases in the field of pediatric surgery. It is well known that the aganglionic bowel is primarily a causative factor of dismotility of distal narrow segment. Recent studies have shown that mutations in endothelin-B receptor (EDNRB), endothelin-3, RET, glial cell line-derived neurotrophic factor (GDNF) genes are responsible for the occurrence of congenital aganglionosis. Here, the authors describe two new mutations of the EDNRB gene in Japanese patients with HD.


RESULTS
One patient had a heterozygous point mutation at the splice donor site of intron 3, leading to premature termination of translation of EDNRB mRNA. Another patient has a heterozygous missense mutation (N1041) in exon 1, but the same mutation was found in two of 50 normal individuals, so the mutation may be a noncausative polymorphism of the EDNRB gene.


CONCLUSIONS
These results provide further evidence that a spectrum of different mutations within the EDNRB gene are responsible for HD.
Department of Pediatric Surgery, Osaka University Medical School, Japan.
M
M
Inoue
K
K
Hosoda
K
K
Imura
S
S
Kamata
M
M
Fukuzawa
K
K
Nakao
A
A
Okada
D001483:Base Sequence; D005260:Female; D015870:Gene Expression; D006627:Hirschsprung Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000235:genetics*; D012680:Sensitivity and Specificity
D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin