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Novel nonsense mutation of the endothelin-B receptor gene in a family with Waardenburg-Hirschsprung disease.
Am J Med Genet. 1999 Nov 05; 87(1):69-71.AJ

Abstract

Waardenburg syndrome (WS) comprises sensorineural hearing loss, hypopigmentation of skin and hair, and pigmentary disturbances of the irides. Four types of WS have been classified to date; in WS type IV (WS4), patients additionally have colonic aganglionosis (Hirschsprung disease, HSCR). Mutations in the endothelin-3 (EDN3), endothelin-B receptor (EDNRB), and Sox10 genes have been identified as causative for WS type IV. We screened a family with a combined WS-HSCR phenotype for mutations in the EDNRB locus using standard DNA mutation analysis and sequencing techniques. We have identified a novel nonsense mutation at codon 253 (CGA-->TGA, Arg-->STOP). This mutation leads to a premature end of the translation of EDNRB at exon 3, and it is predicted to produce a truncated and nonfunctional endothelin-B receptor. All affected relatives were heterozygous for the Arg(253)-->STOP mutation, whereas it was not observed in over 50 unrelated individuals used as controls. These data confirm the role of EDNRB in the cause of the Waardenburg-Hirschsprung syndrome and demonstrate that in WS-HSCR there is a lack of correlation between phenotype and genotype and a variable expression of disease even within the same family.

Authors+Show Affiliations

Medical Genetics Unit, St. George's Hospital Medical School, London, United Kingdom. p.syrris@sghms.ac.ukNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10528251

Citation

Syrris, P, et al. "Novel Nonsense Mutation of the endothelin-B Receptor Gene in a Family With Waardenburg-Hirschsprung Disease." American Journal of Medical Genetics, vol. 87, no. 1, 1999, pp. 69-71.
Syrris P, Carter ND, Patton MA. Novel nonsense mutation of the endothelin-B receptor gene in a family with Waardenburg-Hirschsprung disease. Am J Med Genet. 1999;87(1):69-71.
Syrris, P., Carter, N. D., & Patton, M. A. (1999). Novel nonsense mutation of the endothelin-B receptor gene in a family with Waardenburg-Hirschsprung disease. American Journal of Medical Genetics, 87(1), 69-71.
Syrris P, Carter ND, Patton MA. Novel Nonsense Mutation of the endothelin-B Receptor Gene in a Family With Waardenburg-Hirschsprung Disease. Am J Med Genet. 1999 Nov 5;87(1):69-71. PubMed PMID: 10528251.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel nonsense mutation of the endothelin-B receptor gene in a family with Waardenburg-Hirschsprung disease. AU - Syrris,P, AU - Carter,N D, AU - Patton,M A, PY - 1999/10/21/pubmed PY - 1999/10/21/medline PY - 1999/10/21/entrez SP - 69 EP - 71 JF - American journal of medical genetics JO - Am J Med Genet VL - 87 IS - 1 N2 - Waardenburg syndrome (WS) comprises sensorineural hearing loss, hypopigmentation of skin and hair, and pigmentary disturbances of the irides. Four types of WS have been classified to date; in WS type IV (WS4), patients additionally have colonic aganglionosis (Hirschsprung disease, HSCR). Mutations in the endothelin-3 (EDN3), endothelin-B receptor (EDNRB), and Sox10 genes have been identified as causative for WS type IV. We screened a family with a combined WS-HSCR phenotype for mutations in the EDNRB locus using standard DNA mutation analysis and sequencing techniques. We have identified a novel nonsense mutation at codon 253 (CGA-->TGA, Arg-->STOP). This mutation leads to a premature end of the translation of EDNRB at exon 3, and it is predicted to produce a truncated and nonfunctional endothelin-B receptor. All affected relatives were heterozygous for the Arg(253)-->STOP mutation, whereas it was not observed in over 50 unrelated individuals used as controls. These data confirm the role of EDNRB in the cause of the Waardenburg-Hirschsprung syndrome and demonstrate that in WS-HSCR there is a lack of correlation between phenotype and genotype and a variable expression of disease even within the same family. SN - 0148-7299 UR - https://www.unboundmedicine.com/medline/citation/10528251/Novel_nonsense_mutation_of_the_endothelin_B_receptor_gene_in_a_family_with_Waardenburg_Hirschsprung_disease_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0148-7299&date=1999&volume=87&issue=1&spage=69 DB - PRIME DP - Unbound Medicine ER -