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Association of endothelin-beta receptor (EDNRB) gene variants in anorectal malformations.
J Pediatr Surg. 2007 Jul; 42(7):1266-70.JP

Abstract

Animal models have demonstrated the role of genetic influences in anorectal malformations (ARM), although the pathogenetic mechanism remains uncertain. A body of collateral evidence points to possible connection with the endothelin-beta receptor (EDNRB) gene and the endothelin system. This study investigates the EDNRB gene in patients with ARM. Resected surgical specimens of terminal colonic tissue were obtained from 14 children (6 males and 8 females) undergoing surgery for ARM correction with ethical permission. DNA samples were screened for mutations in EDNRB. Polymerase chain reaction amplification of 7 exons of EDNRB was followed by heteroduplex single-strand conformation polymorphism analysis. Heteroduplex single-strand conformation polymorphism variants were validated with automated sequencing techniques on polymerase chain reaction products showing conformational variants in acrylamide gel. All investigated patients with ARM showed mobility shift aberrations and polymorphisms in the EDNRB gene. These included one previously described polymorphism in exon 4 (831G/A) seen in association with Hirschsprung disease and 6 novel polymorphisms identified in exons 1 (178G/A), 2 (552C/T and 561C/T), and 3 (702C/T). No aberrant banding patterns were observed. The exon 1 (178 G/A) variation was identified in 2 (50%) of 4 low lesions compared with 1 (1%) of 84 control samples. The exon 3 (702C/T) single nucleotide polymorphism was present in 3 (60%) of 5 of the supralevator lesions being associated with exon 4 (831G/A). The patient with VATER associations including cardiac and limb anomalies had the 831G/A variation only. Analysis revealed statistically significant differences for the polymorphism 178G/A (P < .01, chi2 with Yates correction = 8.24) compared to controls. Potential disease-related mutations were identified in South African patients with ARM, raising the question of its potential role in the pathogenesis of this condition.

Authors+Show Affiliations

Division of Paediatric Surgery, Faculty of Medicine, University of Stellenbosch, P.O. Box 19063, Tygerberg 7505, South Africa. swm@sun.ac.zaNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17618893

Citation

Moore, Sam W., and Monique G. Zaahl. "Association of Endothelin-beta Receptor (EDNRB) Gene Variants in Anorectal Malformations." Journal of Pediatric Surgery, vol. 42, no. 7, 2007, pp. 1266-70.
Moore SW, Zaahl MG. Association of endothelin-beta receptor (EDNRB) gene variants in anorectal malformations. J Pediatr Surg. 2007;42(7):1266-70.
Moore, S. W., & Zaahl, M. G. (2007). Association of endothelin-beta receptor (EDNRB) gene variants in anorectal malformations. Journal of Pediatric Surgery, 42(7), 1266-70.
Moore SW, Zaahl MG. Association of Endothelin-beta Receptor (EDNRB) Gene Variants in Anorectal Malformations. J Pediatr Surg. 2007;42(7):1266-70. PubMed PMID: 17618893.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of endothelin-beta receptor (EDNRB) gene variants in anorectal malformations. AU - Moore,Sam W, AU - Zaahl,Monique G, PY - 2007/7/10/pubmed PY - 2007/9/7/medline PY - 2007/7/10/entrez SP - 1266 EP - 70 JF - Journal of pediatric surgery JO - J Pediatr Surg VL - 42 IS - 7 N2 - Animal models have demonstrated the role of genetic influences in anorectal malformations (ARM), although the pathogenetic mechanism remains uncertain. A body of collateral evidence points to possible connection with the endothelin-beta receptor (EDNRB) gene and the endothelin system. This study investigates the EDNRB gene in patients with ARM. Resected surgical specimens of terminal colonic tissue were obtained from 14 children (6 males and 8 females) undergoing surgery for ARM correction with ethical permission. DNA samples were screened for mutations in EDNRB. Polymerase chain reaction amplification of 7 exons of EDNRB was followed by heteroduplex single-strand conformation polymorphism analysis. Heteroduplex single-strand conformation polymorphism variants were validated with automated sequencing techniques on polymerase chain reaction products showing conformational variants in acrylamide gel. All investigated patients with ARM showed mobility shift aberrations and polymorphisms in the EDNRB gene. These included one previously described polymorphism in exon 4 (831G/A) seen in association with Hirschsprung disease and 6 novel polymorphisms identified in exons 1 (178G/A), 2 (552C/T and 561C/T), and 3 (702C/T). No aberrant banding patterns were observed. The exon 1 (178 G/A) variation was identified in 2 (50%) of 4 low lesions compared with 1 (1%) of 84 control samples. The exon 3 (702C/T) single nucleotide polymorphism was present in 3 (60%) of 5 of the supralevator lesions being associated with exon 4 (831G/A). The patient with VATER associations including cardiac and limb anomalies had the 831G/A variation only. Analysis revealed statistically significant differences for the polymorphism 178G/A (P < .01, chi2 with Yates correction = 8.24) compared to controls. Potential disease-related mutations were identified in South African patients with ARM, raising the question of its potential role in the pathogenesis of this condition. SN - 1531-5037 UR - https://www.unboundmedicine.com/medline/citation/17618893/Association_of_endothelin_beta_receptor__EDNRB__gene_variants_in_anorectal_malformations_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-3468(07)00132-7 DB - PRIME DP - Unbound Medicine ER -