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A homozygous mutation in the endothelin-3 gene associated with a combined Waardenburg type 2 and Hirschsprung phenotype (Shah-Waardenburg syndrome).
Nat Genet. 1996 Apr; 12(4):445-7.NGen

Abstract

Hirschsprung disease (HSCR) or colonic aganglionosis is a congenital disorder characterized by an absence of intramural ganglia along variable lengths of the colon resulting in intestinal obstruction. The incidence of HSCR is 1 in 5,000 live births. Mutations in the RET gene, which codes for a receptor tyrosine kinase, and in EDNRB which codes for the endothelin-B receptor, have been shown to be associated with HSCR in humans. The lethal-spotted mouse which has pigment abnormalities, but also colonic aganglionosis, carries a mutation in the gene coding for endothelin 3 (Edn3), the ligand for the receptor protein encoded by EDNRB. Here, we describe a mutation of the human gene for endothelin 3 (EDN3), homozygously present in a patient with a combined Waardenburg syndrome type 2 (WS2) and HSCR phenotype (Shah-Waardenburg syndrome). The mutation, Cys159Phe, in exon 3 in the ET-3 like domain of EDN3, presumably affects the proteolytic processing of the preproendothelin to the mature peptide EDN3. The patient's parents were first cousins. A previous child in this family had been diagnosed with a similar combination of HSCR, depigmentation and deafness. Depigmentation and deafness were present in other relatives. Moreover, we present a further indication for the involvement of EDNRB in HSCR by reporting a novel mutation detected in one of 40 unselected HSCR patients.

Authors+Show Affiliations

Department of Medical Genetics, University of Groningen, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8630503

Citation

Hofstra, R M., et al. "A Homozygous Mutation in the Endothelin-3 Gene Associated With a Combined Waardenburg Type 2 and Hirschsprung Phenotype (Shah-Waardenburg Syndrome)." Nature Genetics, vol. 12, no. 4, 1996, pp. 445-7.
Hofstra RM, Osinga J, Tan-Sindhunata G, et al. A homozygous mutation in the endothelin-3 gene associated with a combined Waardenburg type 2 and Hirschsprung phenotype (Shah-Waardenburg syndrome). Nat Genet. 1996;12(4):445-7.
Hofstra, R. M., Osinga, J., Tan-Sindhunata, G., Wu, Y., Kamsteeg, E. J., Stulp, R. P., van Ravenswaaij-Arts, C., Majoor-Krakauer, D., Angrist, M., Chakravarti, A., Meijers, C., & Buys, C. H. (1996). A homozygous mutation in the endothelin-3 gene associated with a combined Waardenburg type 2 and Hirschsprung phenotype (Shah-Waardenburg syndrome). Nature Genetics, 12(4), 445-7.
Hofstra RM, et al. A Homozygous Mutation in the Endothelin-3 Gene Associated With a Combined Waardenburg Type 2 and Hirschsprung Phenotype (Shah-Waardenburg Syndrome). Nat Genet. 1996;12(4):445-7. PubMed PMID: 8630503.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A homozygous mutation in the endothelin-3 gene associated with a combined Waardenburg type 2 and Hirschsprung phenotype (Shah-Waardenburg syndrome). AU - Hofstra,R M, AU - Osinga,J, AU - Tan-Sindhunata,G, AU - Wu,Y, AU - Kamsteeg,E J, AU - Stulp,R P, AU - van Ravenswaaij-Arts,C, AU - Majoor-Krakauer,D, AU - Angrist,M, AU - Chakravarti,A, AU - Meijers,C, AU - Buys,C H, PY - 1996/4/1/pubmed PY - 1996/4/1/medline PY - 1996/4/1/entrez SP - 445 EP - 7 JF - Nature genetics JO - Nat Genet VL - 12 IS - 4 N2 - Hirschsprung disease (HSCR) or colonic aganglionosis is a congenital disorder characterized by an absence of intramural ganglia along variable lengths of the colon resulting in intestinal obstruction. The incidence of HSCR is 1 in 5,000 live births. Mutations in the RET gene, which codes for a receptor tyrosine kinase, and in EDNRB which codes for the endothelin-B receptor, have been shown to be associated with HSCR in humans. The lethal-spotted mouse which has pigment abnormalities, but also colonic aganglionosis, carries a mutation in the gene coding for endothelin 3 (Edn3), the ligand for the receptor protein encoded by EDNRB. Here, we describe a mutation of the human gene for endothelin 3 (EDN3), homozygously present in a patient with a combined Waardenburg syndrome type 2 (WS2) and HSCR phenotype (Shah-Waardenburg syndrome). The mutation, Cys159Phe, in exon 3 in the ET-3 like domain of EDN3, presumably affects the proteolytic processing of the preproendothelin to the mature peptide EDN3. The patient's parents were first cousins. A previous child in this family had been diagnosed with a similar combination of HSCR, depigmentation and deafness. Depigmentation and deafness were present in other relatives. Moreover, we present a further indication for the involvement of EDNRB in HSCR by reporting a novel mutation detected in one of 40 unselected HSCR patients. SN - 1061-4036 UR - https://www.unboundmedicine.com/medline/citation/8630503/A_homozygous_mutation_in_the_endothelin_3_gene_associated_with_a_combined_Waardenburg_type_2_and_Hirschsprung_phenotype__Shah_Waardenburg_syndrome__ L2 - https://doi.org/10.1038/ng0496-445 DB - PRIME DP - Unbound Medicine ER -