title: Impact of 226C>T MSH2 gene mutation on cancer phenotypes in two HNPCC-associated highly-consanguineous families from Kuwait: emphasis on premarital genetic testing.
abstract: Lynch syndrome or hereditary nonpolyposis colorectal cancer (HNPCC) is one of the commonest cancer susceptibility syndromes. It is characterized by early onset colon cancer and a variety of extracolonic tumours. Germline mutations in the DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS1, and PMS2) are responsible for this disorder. Identifying an affected individual depends on the tumour histopathology, family history that fulfils the Amsterdam and/or Bethesda criteria, tumour immunohistochemistry, microsatellite instability, and finally molecular analysis of an affected member. It is a laborious, time consuming and expensive procedure, which needs the effort of a multi-disciplinary team. However, once the diagnosis is established and germline defect is identified, other high risk pre-symptomatic carriers could be offered intensive surveillance and management as a preventive measure against cancer development. Here, we present two large highly consanguineous HNPCC-families from Kuwait in whom a founder MSH2 mutation was identified. The relationship between this mutation and cancer expressivity in two large consanguineous families harbouring other genetic defects is discussed. Moreover, we shed light on the challenges pertaining to diagnosis, screening, premarital counselling of couples and prenatal diagnosis of offspring with biallelic MSH2 gene mutation.
authors: Kuwait Medical Genetics Centre, Maternity Hospital, 13059 Safat, Kuwait. mj_marafie@yahoo.com
authors: Makia J
authors: MJ
authors: Marafie
authors: Sadiqa
authors: S
authors: Al-Awadi
authors: Fatemah
authors: F
authors: Al-Mosawi
authors: Alaa
authors: A
authors: Elshafey
authors: Waleed
authors: W
authors: Al-Ali
authors: Fahd
authors: F
authors: Al-Mulla
mesh_terms: D000328:Adult; D002648:Child; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D018703:Founder Effect; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D007150:Immunohistochemistry; D007730:Kuwait; D008297:Male; D008875:Middle Aged; D051718:MutS Homolog 2 Protein / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011291:Premarital Examinations
chemical_list: C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein