OMIA 002145-9544 : Colorectal cancer, hereditary nonpolyposis, MLH1-related in Macaca mulatta

Possibly relevant human trait(s) and/or gene(s) (MIM number): 609310

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Dominant

Considered a defect: 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.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
MLH1 mutL homolog 1 Macaca mulatta 2 NC_041755.1 (92414222..92469110) MLH1 Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Colorectal cancer, hereditary nonpolyposis, MLH1-related MLH1 nonsense (stop-gain) 2 Bray et al. (2018): "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" 2018 30108684
Colorectal cancer, hereditary nonpolyposis, MLH1-related MLH1 deletion, small (<=20) 2 g.99,561,829–99,561,830 Brammer et al. (2018): "a heterozygous 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)" 2018 29490919

References


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2018 Brammer, D.W., Gillespie, P.J., Tian, M., Young, D., Raveendran, M., Williams, L.E., Gagea, M., Benavides, F.J., Perez, C.J., Broaddus, R.R., Bernacky, B.J., Barnhart, K.F., Alauddin, M.M., Bhutani, M.S., Gibbs, R.A., Sidman, R.L., Pasqualini, R., Arap, W., Rogers, J., Abee, C.R., Gelovani, J.G. :
MLH1-rheMac hereditary nonpolyposis colorectal cancer syndrome in rhesus macaques. Proc Natl Acad Sci U S A 115:2806-2811, 2018. Pubmed reference: 29490919. DOI: 10.1073/pnas.1722106115.
Dray, B.K., Raveendran, M., Harris, R.A., Benavides, F., Gray, S.B., Perez, C.J., McArthur, M.J., Williams, L.E., Baze, W.B., Doddapaneni, H., Muzny, D.M., Abee, C.R., Rogers, J. :
Mismatch repair gene mutations lead to lynch syndrome colorectal cancer in rhesus macaques. Genes Cancer 9:142-152, 2018. Pubmed reference: 30108684. DOI: 10.18632/genesandcancer.170.

Edit History


  • Created by Frank Nicholas on 26 Mar 2018
  • Changed by Frank Nicholas on 26 Mar 2018
  • Changed by Frank Nicholas on 21 Sep 2018