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Intronic RET gene variants in Down syndrome-associated Hirschsprung disease in an African population.
J Pediatr Surg. 2012 Feb; 47(2):299-302.JP

Abstract

BACKGROUND

Clinical association between Hirschsprung disease (HD) and Down syndrome (DS) is well established. RET promoter and intron 1 variations have been shown to interfere with RET function, increasing the risk of HD pathogenesis. The intronic single-nucleotide polymorphism 2 (SNP2 [rs2435357]) has been associated with DS-associated HD (DS-HD). This study focuses on variations of specific RET intron, 1 SNPs (viz, SNP1 [rs2506004] and SNP2 [rs2435357]) in DS-HD.

PATIENTS AND METHODS

DNA was extracted from paraffin-embedded tissue samples and whole blood in 14 patients with DS with histologically proven HD. Polymerase chain reaction products of RET intron 1 were screened for genetic variation and matched to DS and controls from the general population.

RESULTS

Thirty-seven blood and/or tissue from 14 patients with DS-HD were investigated. RET intronic variations (SNP1 [rs2506004] or SNP2 [rs2435357]) were detected in all patients. SNP1 was detected in all patients, was heterozygous in 9, and homozygous in 5 samples (all aganglionic and 1 total colonic aganglionosis). SNP2 was absent in 6 patients, heterozygous in 6, and homozygous in 3. Three DS controls had a heterozygous SNP1. Homozygous intronic SNP RET variations were related to aganglionic tissue but not normally ganglionated or transitional zone from the same individual.

CONCLUSIONS

Potential disease-related RET mutations were identified in the intron region in 80% of patients with DS-HD investigated, suggesting a causal relationship. The presence of a homozygous form in the aganglionic tissue probably represents a somatic mutation, which suggests local microenvironmental factors in HD pathogenesis.

Authors+Show Affiliations

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

Pub Type(s)

Journal Article

Language

eng

PubMed ID

22325379

Citation

Moore, Samuel W., and Monique G. Zaahl. "Intronic RET Gene Variants in Down Syndrome-associated Hirschsprung Disease in an African Population." Journal of Pediatric Surgery, vol. 47, no. 2, 2012, pp. 299-302.
Moore SW, Zaahl MG. Intronic RET gene variants in Down syndrome-associated Hirschsprung disease in an African population. J Pediatr Surg. 2012;47(2):299-302.
Moore, S. W., & Zaahl, M. G. (2012). Intronic RET gene variants in Down syndrome-associated Hirschsprung disease in an African population. Journal of Pediatric Surgery, 47(2), 299-302. https://doi.org/10.1016/j.jpedsurg.2011.11.018
Moore SW, Zaahl MG. Intronic RET Gene Variants in Down Syndrome-associated Hirschsprung Disease in an African Population. J Pediatr Surg. 2012;47(2):299-302. PubMed PMID: 22325379.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Intronic RET gene variants in Down syndrome-associated Hirschsprung disease in an African population. AU - Moore,Samuel W, AU - Zaahl,Monique G, PY - 2011/11/02/received PY - 2011/11/10/accepted PY - 2012/2/14/entrez PY - 2012/2/14/pubmed PY - 2012/6/29/medline SP - 299 EP - 302 JF - Journal of pediatric surgery JO - J Pediatr Surg VL - 47 IS - 2 N2 - BACKGROUND: Clinical association between Hirschsprung disease (HD) and Down syndrome (DS) is well established. RET promoter and intron 1 variations have been shown to interfere with RET function, increasing the risk of HD pathogenesis. The intronic single-nucleotide polymorphism 2 (SNP2 [rs2435357]) has been associated with DS-associated HD (DS-HD). This study focuses on variations of specific RET intron, 1 SNPs (viz, SNP1 [rs2506004] and SNP2 [rs2435357]) in DS-HD. PATIENTS AND METHODS: DNA was extracted from paraffin-embedded tissue samples and whole blood in 14 patients with DS with histologically proven HD. Polymerase chain reaction products of RET intron 1 were screened for genetic variation and matched to DS and controls from the general population. RESULTS: Thirty-seven blood and/or tissue from 14 patients with DS-HD were investigated. RET intronic variations (SNP1 [rs2506004] or SNP2 [rs2435357]) were detected in all patients. SNP1 was detected in all patients, was heterozygous in 9, and homozygous in 5 samples (all aganglionic and 1 total colonic aganglionosis). SNP2 was absent in 6 patients, heterozygous in 6, and homozygous in 3. Three DS controls had a heterozygous SNP1. Homozygous intronic SNP RET variations were related to aganglionic tissue but not normally ganglionated or transitional zone from the same individual. CONCLUSIONS: Potential disease-related RET mutations were identified in the intron region in 80% of patients with DS-HD investigated, suggesting a causal relationship. The presence of a homozygous form in the aganglionic tissue probably represents a somatic mutation, which suggests local microenvironmental factors in HD pathogenesis. SN - 1531-5037 UR - https://www.unboundmedicine.com/medline/citation/22325379/Intronic_RET_gene_variants_in_Down_syndrome_associated_Hirschsprung_disease_in_an_African_population_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-3468(11)00998-5 DB - PRIME DP - Unbound Medicine ER -