| | |  | | | | Record from Web of Science® | | | | | | |
| A MISSENSE MUTATION OF THE ENDOTHELIN-B RECEPTOR GENE IN MULTIGENIC HIRSCHSPRUNGS-DISEASE |
|
|
| Author(s): PUFFENBERGER EG, HOSODA K, WASHINGTON SS, NAKAO K, DEWIT D, YANAGISAWA M, CHAKRAVARTI A |
| Source: CELL Volume: 79 Issue: 7 Pages: 1257-1266 Published: DEC 30 1994 |
| Times Cited: 572 References: 54 |
| Abstract: Hirschsprung's disease (HSCR) is characterized by an absence of enteric ganglia in the distal colon and a failure of innervation in the gastrointestinal tract. We recently mapped a recessive susceptibility locus (HSCR2) to human chromosome 13q22, which we now demonstrate to be the endothelin-B receptor gene (EDNRB). We identified in HSCR patients a G-->T missense mutation in EDNRB exon 4 that substitutes the highly conserved Trp-276 residue in the fifth transmembrane helix of the G protein-coupled receptor with a Cys residue (W276C). The mutant W276C receptor exhibited a partial impairment of ligand-induced Ca2+ transient levels in transfected cells. The mutation is dosage sensitive, in that W276C homozygotes and heterozygotes have a 74% and a 21% risk, respectively, of developing HSCR. Genotype analysis of patients in a Mennonite pedigree shows HSCR to he a multigenic disorder. |
| Document Type: Article |
| Language: English |
| Reprint Address: PUFFENBERGER, EG (reprint author), CASE WESTERN RESERVE UNIV, SCH MED, DEPT GENET, CLEVELAND, OH 44106 USA |
Addresses:
1. CASE WESTERN RESERVE UNIV, SCH MED, CTR HUMAN GENET, CLEVELAND, OH 44106 USA
2. UNIV CLEVELAND HOSP, CLEVELAND, OH 44106 USA
3. UNIV TEXAS, SW MED CTR, HOWARD HUGHES MED INST, DALLAS, TX 75235 USA
4. UNIV TEXAS, SW MED CTR, DEPT MOLEC GENET, DALLAS, TX 75235 USA
5. KYOTO UNIV, SCH MED, DEPT MED, DIV 2, KYOTO 606, JAPAN |
| Publisher: CELL PRESS, 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: PZ860 |
| ISSN: 0092-8674 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |