Novel mutations in the LKB1/STK11 gene in Dutch Peutz-Jeghers families

The Peutz-Jeghers syndrome (PJS) is a rare hereditary disorder in which gas trointestinal hamartomatous polyposis, mucocutaneous pigmentation, and a pr edisposition for developing cancer are transmitted in an autosomal dominant fashion. The recently identified LKB1/STK11 gene located at chromosome 19p 13.3 is mutated in a number of PJS pedigrees, We performed mutation analysi s in 19, predominantly Dutch, PJS families. In 12 of these families, we ide ntified LKB1/STK11 mutations, none of which has been described before. Thes e 12 novel LKB1/STK11 mutations consist of one nonsense mutation, three fra meshift deletions, three frameshift insertions, two acceptor splice site mu tations, and three missense mutations. In addition, we detected four polymo rphisms in LKB1/STK11. In the remaining seven PJS families, we found no app arent abnormalities of the LKB1/STK11 gene, which could reflect the existen ce of locus heterogeneity in PJS, None of the mutations occurred in more th an one family, and a number were demonstrated to have arisen de novo, The d iverse array of mutations found, the apparent high mutation rate, as well a s the existence of a possible second PJS locus, renders diagnostic or predi ctive genetic testing in individual patients difficult, although future ide ntification of additional mutations or even gene(s) will help in increasing the yield of direct mutation analysis. Hum Mutat 13:476-481, 1999. (C) 199 9 Wiley-Liss, Inc.