ArticleAmerican journal of human genetics2003
A founding locus within the RET proto-oncogene may account for a large proportion of apparently sporadic Hirschsprung disease and a subset of cases of sporadic medullary thyroid carcinoma.
Article in American journal of human genetics, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 102 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
- mRNA sequencing provides new insights into the pathogenesis of Hirschsprung's disease in mice.Pediatric surgery international · 2023Article
- Analysis of a pedigree of Peutz-Jeghers syndrome andTranslational cancer research · 2020Article
- Negative Association Between lncRNAPharmacogenomics and personalized medicine · 2020Article
- Two Novel SNPs inAnimals : an open access journal from MDPI · 2019Article
- Effect of 3'UTR RET Variants on RET mRNA Secondary Structure and Disease Presentation in Medullary Thyroid Carcinoma.PloS one · 2016Article
- Exome sequencing reveals a high genetic heterogeneity on familial Hirschsprung disease.Scientific reports · 2015Article
- Next-generation-based targeted sequencing as an efficient tool for the study of the genetic background in Hirschsprung patients.BMC medical genetics · 2015Article
- KIT Mutation and Loss of 14q May Be Sufficient for the Development of Clinically Symptomatic Very Low-Risk GIST.PloS one · 2015Article
- Pathways systematically associated to Hirschsprung's disease.Orphanet journal of rare diseases · 2013Article
- Mutational spectrum of semaphorin 3A and semaphorin 3D genes in Spanish Hirschsprung patients.PloS one · 2013Article
- Four new loci associations discovered by pathway-based and network analyses of the genome-wide variability profile of Hirschsprung's disease.Orphanet journal of rare diseases · 2012Article
- Molecular basis of medullary thyroid carcinoma: the role of RET polymorphisms.International journal of molecular sciences · 2012Review
- RET haplotype, not linked to the C620R activating mutation, associated with Hirschsprung disease in a novel MEN2 family.Clinics (Sao Paulo, Brazil) · 2012Review
- Comprehensive analysis of RET common and rare variants in a series of Spanish Hirschsprung patients confirms a synergistic effect of both kinds of events.BMC medical genetics · 2011Article
- MYH biallelic mutation can inactivate the two genetic pathways of colorectal cancer by APC or MLH1 transversions.Familial cancer · 2010Article
- Novel association of severe neonatal encephalopathy and Hirschsprung disease in a male with a duplication at the Xq28 region.BMC medical genetics · 2010Article
- Novel MLPA procedure using self-designed probes allows comprehensive analysis for CNVs of the genes involved in Hirschsprung disease.BMC medical genetics · 2010Article
- Genetic basis of Hirschsprung's disease.Pediatric surgery international · 2009Review
- RET polymorphisms and the risk of Hirschsprung's disease in a Chinese population.Journal of human genetics · 2008Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
Hirschsprung disease (HSCR) is a common congenital disorder characterized by aganglionosis of the gut. The seemingly unrelated multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant disorder characterized by medullary thyroid carcinoma (MTC), pheochromocytoma, and hyperparathyroidism. Yet, germline mutations in the RET proto-oncogene are associated with both MEN 2 and HSCR. In the former, gain-of-function mutations in a limited set of codons is found, whereas, in the latter, loss-of-function mutations are found. However, germline RET mutation is associated with only 3% of a population-based series of isolated HSCR, and little is known about susceptibility to sporadic MTC. We have found previously that specific haplotypes comprising RET coding single-nucleotide polymorphisms (SNPs) comprising exon 2 SNP A45A were strongly associated with HSCR, whereas haplotypes associated with exon 14 SNP S836S were associated with MTC. In this study, we describe three novel intron 1 SNPs, and, together with the coding SNP haplotypes, the data suggest the presence of distinct ancestral haplotypes for HSCR and sporadic MTC in linkage disequilibrium with a putative founding susceptibility locus/loci. The data are consistent with the presence of a very ancient, low-penetrance founder locus approximately 20-30 kb upstream of SNP A45A, but the failure of the SNPs to span the locus presents challenges in modeling mode of transmission or ancestry. We postulate that this founding locus is germane to both isolated HSCR and MTC but also that different mutations in this locus would predispose to one or the other.
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