Categories: Neoplasm

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 609310 (trait) , 120436 (gene)

Links to relevant human diseases in MONDO:

• MONDO:0012249: colorectal cancer, hereditary nonpolyposis, type 2

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal dominant

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2018

Cross-species summary: Lynch syndrome; HNPCC2

Species-specific symbol: MLH1-rheMac

Molecular basis: Brammer et al. (2018) reported that "current results provide supportive evidence for the existence of HNPCC (MLH1-rheMac syndrome) in rhesus macaques resulting from the loss of MLH1 protein expression, which represents a simian ortholog of Lynch syndrome in humans. The loss of MLH1 expression is potentially due to several reasons, including a deletion mutation in the MLH1 promoter region, which results in decreased transcriptional activity." These authors identified the likely causal variant as a "deletion in the putative promoter region of the MLH1 gene (rheMac2: 2:99,561,829–99,561,830; hg19: ∼3:37,034,780; c.−258_259)". Dray et al. (2018) reported a likely causal variant as "a de novo stop codon in the coding region of MLH1. This de novo stop codon occurs in exon 11 out of 19 in the MLH1 gene, and thus would produce a dramatically truncated and possibly non-functional protein". These authors did not provide any details on this variant. Ozirmak Lermi et al. (2022) report that a "cohort of rhesus macaques from our institution developed spontaneous mismatch repair deficient (MMRd) CRC with a notable fraction harboring a pathogenic germline mutation in MLH1 (c.1029C

Associated gene: