R659X mutation in the MLH1 gene in hereditary non-polyposis colorectal cancer (HNPCC) in an Indian extended family.

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dc.contributor.authorSingh, Rajender
dc.contributor.authorSingh, Pooja
dc.contributor.authorKumar, M V Kranthi
dc.contributor.authorKarwasra, Rajendra
dc.contributor.authorSingh, Lalji
dc.contributor.authorThangaraj, Kumarasamy
dc.date.accessioned2011-11-22T06:00:30Z
dc.date.available2011-11-22T06:00:30Z
dc.date.issued2010-01
dc.description.abstractBackground & objective: Hereditary non-polyposis colorectal cancer (HNPCC or Lynch syndrome), is a genetically heterogeneous disorder that is believed to account for 2–10 per cent of all the colorectal cancer cases. The disease follows autosomal dominant inheritance pattern with high penetrance (85%) and younger age of onset when compared to patients with sporadic tumours. HNPCC is associated with germ-line mutations in the DNA mismatch repair (MMR) genes namely MLH1, MSH2, MSH6, and PMS2. The present study was aimed at analyzing mismatch repair gene(s) in an extended Indian family satisfying the Amsterdam criteria, and extending the analysis to general population to estimate frequency of the mutations/polymorphisms observed. Methods: A total 12 members of the HNPCC family were studied for genetic investigation. Ethnically matched 250 normal individuals were also included as controls to study the observed mutations/ polymorphisms at population level. Results: The analysis resulted in identification of a 1975C>T mutation in exon 17, resulting in substitution of arginine residue with stop codon at codon 659. 655A>G substitution was also observed, resulting in replacement of isoleucine with valine at codon 219. Similar analysis on 250 ethnically matched control subjects revealed complete absence of R659X mutation, while I219V variant was found in 9.8 per cent of the controls. Interpretation & conclusion: R659X mutation correlates with disease phenotype, and 655A>G locus is highly polymorphic. Our study suggested that R659X substitution was prime cause for the disease phenotype in this family. I219V substitution is a polymorphism having no association with the disease onset or segregation. The family members harbouring this mutation were advised to be under regular medical surveillance.en_US
dc.identifier.citationSingh Rajender, Singh Pooja, Kumar M V Kranthi, Karwasra Rajendra, Singh Lalji, Thangaraj Kumarasamy. R659X mutation in the MLH1 gene in hereditary non-polyposis colorectal cancer (HNPCC) in an Indian extended family. Indian Journal of Medical Research. 2010 Jan; 131(1): 64-70.en_US
dc.identifier.urihttps://imsear.searo.who.int/handle/123456789/135408
dc.language.isoenen_US
dc.source.urihttps://icmr.nic.in/ijmr/2010/january/0107.pdfen_US
dc.subjectcolorectal canceren_US
dc.subjectgastric canceren_US
dc.subjectHNPCCen_US
dc.subjectLynch syndromeen_US
dc.subjectMLH1 geneen_US
dc.subject.meshAdaptor Proteins, Signal Transducing --genetics
dc.subject.meshAged
dc.subject.meshBase Pair Mismatch
dc.subject.meshBase Sequence
dc.subject.meshColorectal Neoplasms, Hereditary Nonpolyposis --genetics
dc.subject.meshDNA Primers
dc.subject.meshDNA Repair --genetics
dc.subject.meshExons
dc.subject.meshFemale
dc.subject.meshHumans
dc.subject.meshIndia
dc.subject.meshMale
dc.subject.meshMiddle Aged
dc.subject.meshMutation
dc.subject.meshNuclear Proteins --genetics
dc.subject.meshPedigree
dc.titleR659X mutation in the MLH1 gene in hereditary non-polyposis colorectal cancer (HNPCC) in an Indian extended family.en_US
dc.typeArticleen_US
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