ArticleProceedings of the National Academy of Sciences of the United States of America2000
A human model for multigenic inheritance: phenotypic expression in Hirschsprung disease requires both the RET gene and a new 9q31 locus.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 209 citations in OpenAlex.
- Combinatorial multiomic analysis from a pedigree of Sox10Dom Hirschsprung mice identifies multiple high confidence candidate modifiers of Enteric Nervous System development.PLoS computational biology · 2026Article
- The inactive X chromosome as a female protector in autism and beyond.Nature genetics · 2026Review
- Combinatorial multiomic analysis from a pedigree of Sox10bioRxiv : the preprint server for biology · 2025Article
- The inactive X chromosome as a female protector in autism and beyond.Research square · 2025Article
- Comprehensive characterization of the genetic landscape of familial Hirschsprung's disease.World journal of pediatrics : WJP · 2023Review
- A Single RET Mutation in Hirschsprung Disease Induces Intestinal Aganglionosis Via a Dominant-Negative Mechanism.Cellular and molecular gastroenterology and hepatology · 2023Article
- Novel CausativeJournal of pediatric genetics · 2022Article
- Distribution of RET proto-oncogene variants in children with appendicitis.Molecular genetics & genomic medicine · 2022Article
- Genetic Background Influences Severity of Colonic Aganglionosis and Response to GDNF Enemas in theInternational journal of molecular sciences · 2021Article
- Role of Glycans on Key Cell Surface Receptors That Regulate Cell Proliferation and Cell Death.Cells · 2021Review
- Genetic variants inAging · 2020Article
- Copy number variations in candidate genomic regions confirm genetic heterogeneity and parental bias in Hirschsprung disease.Orphanet journal of rare diseases · 2019Article
- Sequence characterization of RET in 117 Chinese Hirschsprung disease families identifies a large burden of de novo and parental mosaic mutations.Orphanet journal of rare diseases · 2019Article
- Functional Studies on NovelFrontiers in genetics · 2019Article
- Advances in understanding the association between Down syndrome and Hirschsprung disease (DS-HSCR).Pediatric surgery international · 2018Review
- Exome-Wide Association Study Identified New Risk Loci for Hirschsprung's Disease.Molecular neurobiology · 2017Article
- Hirschsprung's disease: clinical dysmorphology, genes, micro-RNAs, and future perspectives.Pediatric research · 2017Review
- Transcriptional Dynamics at Brain Enhancers: from Functional Specialization to Neurodegeneration.Current neurology and neuroscience reports · 2016Review
- Detection and preliminary screening of the human gene expression profile for Hirschsprung's disease.Molecular medicine reports · 2016Article
- Exome sequencing reveals a high genetic heterogeneity on familial Hirschsprung disease.Scientific reports · 2015Article
15 more citing papers are in PubMed but not listed here.
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9 authors at 4 institutions in 3 countries.
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Abstract
Reduced penetrance in genetic disorders may be either dependent or independent of the genetic background of gene carriers. Hirschsprung disease (HSCR) demonstrates a complex pattern of inheritance with approximately 50% of familial cases being heterozygous for mutations in the receptor tyrosine kinase RET. Even when identified, the penetrance of RET mutations is only 50-70%, gender-dependent, and varies with the extent of aganglionosis. We searched for additional susceptibility genes which, in conjunction with RET, lead to phenotypic expression by studying 12 multiplex HSCR families. Haplotype analysis and extensive mutation screening demonstrated three types of families: six families harboring severe RET mutations (group I); and the six remaining families, five of which are RET-linked families with no sequence alterations and one RET-unlinked family (group II). Although the presence of RET mutations in group I families is sufficient to explain HSCR inheritance, a genome scan reveals a new susceptibility locus on 9q31 exclusively in group II families. As such, the gene at 9q31 is a modifier of HSCR penetrance. These observations imply that identification of new susceptibility factors in a complex disease may depend on classification of families by mutational type at known susceptibility genes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.