TY - JOUR T1 - A missense mutation in both <em>hMSH2</em> and<em>APC</em> in an Ashkenazi Jewish HNPCC kindred: implications for clinical screening JF - Journal of Medical Genetics JO - J Med Genet SP - 792 LP - 793 DO - 10.1136/jmg.36.10.792 VL - 36 IS - 10 AU - ZHI QIANG YUAN AU - NORA WONG AU - WILLIAM D FOULKES AU - LESLEY ALPERT AU - FORTUNATO MANGANARO AU - CORINNE ANDREUTTI-ZAUGG AU - RICHARD IGGO AU - KIRA ANTHONY AU - EUGENE HSIEH AU - MARK REDSTON AU - LEONARD PINSKY AU - MARK TRIFIRO AU - PHILIP H GORDON AU - DANA LASKO Y1 - 1999/10/01 UR - http://jmg.bmj.com/content/36/10/792.abstract N2 - Editor—Colorectal carcinoma (CRC), among the most common neoplasms in humans, has a moderately large hereditary component. The two most frequent hereditary CRC syndromes are hereditary non-polyposis colorectal cancer (HNPCC) and familial adenomatous polyposis (FAP), both dominantly inherited disorders. HNPCC is caused by inherited defects in the DNA mismatch repair (MMR) geneshMLH1, hMSH2,PMS1, and PMS2; FAP is caused by mutations in the APCgene.1 Between 1 and 4% of all CRC fully satisfy the international criteria for HNPCC.2-4 In addition to CRC, these families also have an excess incidence of adenocarcinoma of the endometrium and to a lesser degree, cancer of the stomach, ovary, and other sites.5 Alterations inhMSH2 or hMLH1account for ∼90% of the germline mutations detected in HNPCC.1 Mutations in hMSH6 have been described in CRC kindreds that resemble HNPCC but do not always fulfil the above mentioned criteria.6 ,7 Familial adenomatous polyposis (FAP) accounts for less than 1% of CRC; it is characterised by the development of a large number (&gt;100) of colorectal polyps, which, if untreated, will inevitably lead to CRC.8 The gene underlying FAP,APC, was identified in 1991; germline mutations truncating the APC gene product are usually found in FAP.9 ,10 An interesting missense variant in APC, I1307K, was discovered in a 39 year old man with eight colorectal polyps11 with a family history of colorectal polyps and CRC but not FAP. The T to A polymorphism at nt 3920 in APC was postulated to predispose to cancer, not as a direct effect of the protein, but by rendering its region of APChypermutable. The mutation does not seem to be common in populations other than Ashkenazi Jews, where it is found at a … ER -