本文選題：黑斑息肉綜合征 + STK11基因�。� 參考：《川北醫(yī)學院》2015年碩士論文

【摘要】：研究背景:黑斑息肉綜合征,即PJ綜合征(波伊茨-耶格綜合征,Peutz-Jeghers syndrome,PJS,OMIM 175200),是一種臨床上少見的常染色體顯性遺傳性疾病。臨床主要表現(xiàn)為皮膚粘膜色素沉著性黑斑及胃腸道息肉,又被稱為口周色素沉著(腸)息肉綜合征(perioral pigmentationintestinal polyposis syndrome)。胃腸道息肉以錯構(gòu)瘤或腺瘤為主要病理類型,息肉可能會引起貧血、腹痛、腸梗阻、腸套疊等并發(fā)癥,同時伴有高風險的胃腸或胃腸以外的惡性腫瘤。目前已確定STK11基因為PJ綜合征的致病基因,該基因定位于19號染色體短臂13.3區(qū)域,編碼絲氨酸/蘇氨酸蛋白激酶(serine/threonine kinase LKB1/STK11),其作用是對細胞增殖、極性、功能和能量代謝等方面進行調(diào)控。STK11基因作為一種抑癌基因普遍存在于多種類型的惡性腫瘤之中。目前STK11基因新的突變在不斷地被報道,不但豐富了STK11基因的突變譜,也為基因型和表型的相關(guān)性研究奠定了良好的理論基礎(chǔ)。本研究收集中國四川省漢族人PJ綜合征的3個家系和2個散發(fā)病例的臨床資料,并對患者及其表型正常家庭成員采用DNA直接測序法進行STK11基因的突變檢測。目的:分析中國四川省漢族人黑斑息肉綜合征3個家系和2個散發(fā)病例的臨床特點,檢測STK11基因,發(fā)現(xiàn)新的致病突變。方法:收集3個PJS家系和2個散發(fā)病例詳細的臨床資料,采集PJS患者及其家庭成員的外周血標本,提取外周血細胞中的DNA,對STK11基因的全部外顯子編碼區(qū)及側(cè)翼序列采用聚合酶鏈反應(yīng)法(PCR)進行擴增,并通過對PCR產(chǎn)物使用DNA直接測序法進行序列分析,尋找新的致病突變。結(jié)果:在PJS家系中發(fā)現(xiàn)了2個新的雜合錯義突變。家系1患者的STK11基因7號外顯子發(fā)現(xiàn)c.908TG(p.Ile303Ser)錯義突變。家系2患者的STK11基因9號外顯子發(fā)現(xiàn)c.1251GT(p.Ala417Ser)錯義突變。檢測2個家系其他表型正常的家庭成員及100例無親緣關(guān)系的正常個體,沒有發(fā)現(xiàn)相應(yīng)位點的突變。家系1和家系3患者的STK11基因7號內(nèi)含子均發(fā)現(xiàn)1個雜合c.920+7GC多態(tài)位點(SNP)。散發(fā)病例沒有發(fā)現(xiàn)STK11基因的突變。結(jié)論:研究結(jié)果顯示家系1和家系2患者發(fā)病及出現(xiàn)惡變可能為STK11基因的c.908TG(p.Ile303Ser)和c.1251GT(p.Ala417Ser)2個錯義突變所致。該研究發(fā)現(xiàn)了2個新的錯義突變,豐富了STK11基因突變數(shù)據(jù)庫的突變譜,為家系1和家系3患者的后代開展遺傳咨詢、基因診斷及產(chǎn)前診斷奠定了堅實的基礎(chǔ)。
[Abstract]:Background: PJ syndrome, Peutz-Jeghers syndrome, PJSOMIM 175200, is a rare autosomal dominant hereditary disease. The clinical manifestations are pigmented melanoma and gastrointestinal polyp, also known as perioral pigmentationintestinal polyposis syndrome. The main pathological types of gastrointestinal polyps are hamartoma or adenoma. Polyps may cause anemia, abdominal pain, intestinal obstruction, intussusception and other complications, accompanied by high-risk gastrointestinal or non-gastrointestinal malignancies. The STK11 gene, which is located in the short arm 13.3 region of chromosome 19, encodes serine / threonine protein kinase serine / threonine kinase LKB1 / STK11, which is responsible for cell proliferation and polarity. As a tumor suppressor gene, STK11 gene is widely used in many types of malignant tumors. At present, new mutations of STK11 gene have been reported, which not only enrich the mutation profile of STK11 gene, but also lay a good theoretical foundation for the study of genotype and phenotypic correlation. In this study, the clinical data of 3 families and 2 sporadic cases of PJ syndrome in Han nationality of Sichuan Province, China were collected, and the mutation of STK11 gene was detected by DNA direct sequencing in patients and their normal phenotypic family members. Objective: to analyze the clinical characteristics of 3 families and 2 sporadic cases of black spot polyposis syndrome in Han nationality of Sichuan province of China, and to detect STK11 gene and find a new pathogenic mutation. Methods: the clinical data of 3 PJS families and 2 sporadic cases were collected. The peripheral blood samples of PJS patients and their family members were collected. DNA was extracted from peripheral blood cells and all exon coding regions and flanking sequences of STK11 gene were amplified by polymerase chain reaction (PCR). Results: two new heterozygous missense mutations were found in PJS pedigree. The missense mutation of exon 7 of STK11 gene was found in pedigree 1 patients. A missense mutation of exon 9 of STK11 gene was found in pedigree 2 patients. Two families with normal phenotypes and 100 unrelated normal individuals were detected and no mutation at the corresponding loci was found. A heterozygous c.9207GC polymorphism locus SNPN was found in intron 7 of STK11 gene in both pedigree 1 and pedigree 3. No mutation in STK 11 gene was found in sporadic cases. Conclusion: the results showed that the incidence and malignant change of family 1 and 2 patients were probably caused by two missense mutations of STK11 gene, c.908TGG, Ile303Serand c.1251GTp.Ala417Ser. This study found two new missense mutations, enriched the mutation spectrum of STK11 gene mutation database, and laid a solid foundation for genetic counseling, gene diagnosis and prenatal diagnosis for the offspring of family 1 and family 3 patients.
【學位授予單位】：川北醫(yī)學院
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R596

【參考文獻】

相關(guān)期刊論文 前3條

1 戴益琛;謝軍培;曾偉;傅玉卡;陳章興;;中國大陸黑斑息肉綜合征臨床薈萃分析[J];臨床內(nèi)科雜志;2008年08期

2 呂學霞;蔡豐波;，

本文編號：2009956