ArticleJournal of medical genetics2006
Mutations of the RET gene in isolated and syndromic Hirschsprung's disease in human disclose major and modifier alleles at a single locus.
Article in Journal of medical genetics, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- ASSOCIATION OF RS2435357 AND RS1800858 POLYMORPHISMS IN RET PROTO-ONCOGENE WITH HIRSCHSPRUNG DISEASE: SYSTEMATIC REVIEW AND META-ANALYSIS.Arquivos brasileiros de cirurgia digestiva : ABCD = Brazilian archives of digestive surgery · 2019Pooled it
- From bench to bedside: an interdisciplinary journey through the gut-lung axis with insights into lung cancer and immunotherapy.Frontiers in immunology · 2024Review
- Size matters: Large copy number losses in Hirschsprung disease patients reveal genes involved in enteric nervous system development.PLoS genetics · 2021Article
- Goldberg-Shprintzen syndrome is determined by the absence, or reduced expression levels, of KIFBP.Human mutation · 2020Article
- Advances in understanding the association between Down syndrome and Hirschsprung disease (DS-HSCR).Pediatric surgery international · 2018Review
- Identifying key genes associated with Hirschsprung's disease based on bioinformatics analysis of RNA-sequencing data.World journal of pediatrics : WJP · 2017Article
- Differential expression of FOXA1, DUSP6, and HA117 in colon segments of Hirschsprung's disease.International journal of clinical and experimental pathology · 2015Article
- Chromosomal and related Mendelian syndromes associated with Hirschsprung's disease.Pediatric surgery international · 2012Review
- Genetic interactions and modifier genes in Hirschsprung's disease.World journal of gastroenterology · 2011Review
- PHOX2B mutations in patients with Ondine-Hirschsprung disease and a review of the literature.European journal of pediatrics · 2011Article
- Genetic background impacts developmental potential of enteric neural crest-derived progenitors in the Sox10Dom model of Hirschsprung disease.Human molecular genetics · 2010Article
- Epistasis between RET and BBS mutations modulates enteric innervation and causes syndromic Hirschsprung disease.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
- Genetic model system studies of the development of the enteric nervous system, gut motility and Hirschsprung's disease.Neurogastroenterology and motility · 2009Review
- Linkage proof for PTPN22, a rheumatoid arthritis susceptibility gene and a human autoimmunity gene.Proceedings of the National Academy of Sciences of the United States of America · 2007Article
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn Hirschsprung's disease (HSCR), a hypomorphic allele of a major gene, RET, accounts for most isolated (non-syndromic) cases, along with other autosomal susceptibility loci under a multiplicative model. However, some syndromic forms of HSCR are monogenic entities, for which the disease causing gene is known.
objectiveTo determine whether RET could be considered a modifier gene for the enteric phenotype on the background of a monogenic trait.
methodsThe syndromic HSCR entities studied were congenital central hypoventilation (CCHS) and Mowat-Wilson syndrome (MWS), caused by PHOX2B and ZFHX1B gene mutations, respectively. The RET locus was genotyped in 143 CCHS patients, among whom 44 had HSCR, and in 30 MWS patients, among whom 20 had HSCR. The distribution of alleles, genotypes, and haplotypes was compared within the different groups. To test the interaction in vivo, heterozygous mice were bred for a null allele of Phox2b and Ret genes.
resultsRET was shown to act as a modifier gene for the HSCR phenotype in patients with CCHS but not with MWS. The intestine of double heterozygote mice was indistinguishable from their littermates. A loss of over 50% of each gene function seemed necessary in the mouse model for an enteric phenotype to occur.
conclusionsIn CCHS patients, the weak predisposing haplotype of the RET gene can be regarded as a quantitative trait, being a risk factor for the HSCR phenotype, while in MWS, for which the HSCR penetrance is high, the role of the RET predisposing haplotype is not significant. It seems likely that there are both RET dependent and RET independent HSCR cases.
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