Mutations Of STK11 And FHIT Genes Of Patients With Peutz-Jeghers Syndrome

Peutz-Jeghers syndrome(PJS) is an autosomal dominant disorder characterized by mucocutaneous melanocytic macules, gastrointestinal hamartomatous polyposis and an increased risk of various neoplasms. About 50 percent of patients have a family history of PJS, and the incidence rate was about 1 in 200 000. Germline mutations in the serine/threonine kinase 11(STK11) gene have been identified as a main cause for PJS, which include gene loss of heterozygosity, frameshift mutations or nonsense mutations, etal, resulting in the loss of STK11 gene function. While, still some other patients have no STK11 gene mutation, which indicates that PJS pstients have other mutation genes but STK11 gene, or insist other unknow STK11 gene mutations. Researchers suggested fragile histidine triad(FHIT) gene took part in the development of PJS, which still needs more patients to be investigated in the future research. While there had little researches indicated the relationship of FHIT with PJS, it still needs futher research to confirm whether FHIT gene has relation with the development of PJS, or there are other unknown genes or denovo mutations of STK11 gene. So, more gene mutations or mutation genes will be found, and the genetic heterogeneity will be reduced with the improvement of genetic testing technology, which can futher improve the gene mutation spectrum. The aim of this study was to identify the point mutations in STK11 and FHIT gene coding regions in 36 patients with PJS by analyzing the sequences of STK11 and FHIT gene coding regions using PCR and DNA sequencing, then compared the results with the normal sequence of STK11 and FHIT gene, obtained the novel gene mutations, which will reveal the relationship between the variant of STK11 and FHIT gene in PJS, then will compare the mutation rate between patients with family history and sporadic cases.The result was that: of the 36 patients with PJS, 22 showed STK11 gene mutations in the coding region, including 3 patients with the common mutations and 19 patients with a single mutation site. The remaining 14 patients had no mutations in STK11 gene coding regions. Of the 22 patients with STK11 gene mutations, 7 kinds of mutations were concluded by SNP database, 4 kinds of mutations were reported by researchers, and the other 11 kinds of mutations were considered as denovo mutations. The gene mutation rate of patients with family history was 33.3%, while that of sporadic cases was 50.0%(P=0.50, P>0.05, there is no significant difference). The truncated mutation rate of STK11 gene in patients with family history was 27.8%, which was similar with that in sporadic cases(P=1.00, P>0.05, there is no significant difference). And there is no significant difference in the patients with family history and with sporadic cases at the age of fist mucocutaneous pigmentations and fist laparotomy(P=0.748/0.458, P>0.05). The number of operations was larger in patients with truncated mutations than that in other patients with other mutations(P=0.033/0.038, P<0.05). One patient with truncated mutation of STK11 gene had adenoma polyp. Of the patients with FHIT gene mutations, 1 patient had the mission mutation in non-coding region, and 10 patients showed mutations of nucleotide polymorphism in coding regions,which had been reported before, and it still needs deeper research to confirm whether it participates in the development of PJS by regulating the coding regions. All the patients with STK11 gene mutations had no mutations of FHIT gene.Over all, we conclude that mutations of STK11 gene is a major cause of PJS. The missense and truncated mutations newly found are the novel mutations associated with Peutz-Jeghers syndrome. FHIT gene may participate in the development of PJS. The patients with truncated mutations should be checked with endoscopy or other methods at a early age in case of laparotomy for their more operation times than other patients, which will improve the quality of life to patients with PJS, and lay the foundation of deeper research to the relationship of truncated mutation in STK11 gene and growth and canceration of PJP.