ArticleGenetics in medicine : official journal of the American College of Medical Genetics2019
Biallelic germline nonsense variant of MLH3 underlies polyposis predisposition.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 2 of them syntheses that pooled it.
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Who cites it
38 citing papers in PubMed, 2 syntheses or guidelines pooled it, 60 citations in OpenAlex.
- Japanese society for cancer of the colon and rectum (JSCCR) guidelines 2024 for the clinical practice of hereditary colorectal cancer.International journal of clinical oncology · 2026Guideline
- Updated European guidelines for clinical management of familial adenomatous polyposis (FAP), MUTYH-associated polyposis (MAP), gastric adenocarcinoma, proximal polyposis of the stomach (GAPPS) and other rare adenomatous polyposis syndromes: a joint EHTG-ESCP revision.The British journal of surgery · 2024Guideline
- The 'other' colonic polyposis syndromes-evolving insights and guidance for endoscopists.International journal of colorectal disease · 2026Review
- Familial Adenomatous Polyposis-Risk of Cancer, Cancer Prevention, and Long-Term Consequences: Learnings from Five Decades with the Danish Polyposis Register.APMIS : acta pathologica, microbiologica, et immunologica Scandinavica · 2026Review
- Maternal MLH3 dysfunction drives unexplained recurrent pregnancy loss via impaired oocyte maturation and defective decidualization.Cellular and molecular life sciences : CMLS · 2026Article
- A case of homozygous germline mutation at the MLH3 splicing site causing infertility, colon polyposis with synchronous multiple colon cancers, and osteoma.Gastroenterology report · 2026Article
- The genetic puzzle of FAP: exploring novel diagnostic approaches for APC/MUTYH-negative case.Hereditary cancer in clinical practice · 2025Review
- Long-read DNA and RNA sequencing for inherited polyposis and colorectal cancer: cryptic intronic variants and multiple mutational mechanisms.Journal of medical genetics · 2025Article
- Genetic predisposition to polyposis syndromes.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- Genetics, genomics and clinical features of adenomatous polyposis.Familial cancer · 2025Review
- Uncovering the genetic variation spectrum of colorectal polyposis from a multicentre cohort in China.NPJ precision oncology · 2025Article
- Predictive modeling for the germline pathogenic variant of the APC gene in patients with adenomatous polyposis: proposing a new APC score.Surgery today · 2025Article
- Hereditary Colorectal Cancer: Clinical Implications of Genomic Medicine and Precision Oncology.Journal of the anus, rectum and colon · 2025Review
- Novel insights into tumorigenesis revealed by molecular analysis of Lynch syndrome cases with multiple colorectal tumors.Frontiers in oncology · 2024Article
- Genotype-Phenotype Correlations in Autosomal Dominant and Recessive APC Mutation-Negative Colorectal Adenomatous Polyposis.Digestive diseases and sciences · 2023Review
- Review
- The complementary roles of genome-wide approaches in identifying genes linked to an inherited risk of colorectal cancer.Hereditary cancer in clinical practice · 2023Review
- Genetic Predisposition to Colorectal Cancer: How Many and Which Genes to Test?International journal of molecular sciences · 2023Review
- Lynch syndrome cancer vaccines: A roadmap for the development of precision immunoprevention strategies.Frontiers in oncology · 2023Review
- Hereditary Colorectal Cancer Syndromes: Molecular Genetics and Precision Medicine.Biomedicines · 2022Review
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeSome 10% of familial adenomatous polyposis (FAP) and 80% of attenuated polyposis (AFAP) cases remain molecularly unexplained. We scrutinized such cases by exome-wide and targeted methods to search for novel susceptibility genes.
methodsExome sequencing was conducted on 40 unexplained (mainly sporadic) cases with FAP or AFAP from Finland. The DNA mismatch repair (MMR) gene MLH3 (MutL Homolog 3) was pinpointed and prompted a subsequent screen of ~1000 Swedish patients referred to clinical panel sequencing for colon tumor susceptibility.
resultsThree homozygous carriers of a truncating variant in MLH3, c.3563C>G, p.Ser1188Ter, were identified among the index cases from the Finnish series. An additional biallelic carrier of the same variant was present in the Swedish series. All four patients shared a 0.8-Mb core haplotype around MLH3, suggesting a founder variant. Colorectal polyps from variant carriers showed no instability at mono-, di-, tri-, or tetranucleotide repeats, in agreement with previous findings of a minor role of MLH3 in MMR. Multiple loci were affected by loss of heterozygosity, suggesting chromosomal instability.
conclusionOur results show that a biallelic nonsense variant of MLH3 underlies a novel syndrome with susceptibility to classical or attenuated adenomatous polyposis and possibly extracolonic tumors, including breast cancer.
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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.