反向痤疮一家系调查与致病基因突变分析

发布时间：2018-03-14 17:47

本文选题：反向痤疮　切入点：系谱　出处：《华中科技大学》2012年硕士论文　论文类型：学位论文

【摘要】：目的：研究一个反向痤疮家系的临床特征及其致病基因的突变类型。方法：依据门诊确诊的先证者而追溯到一个反向痤疮三代家系，然后对该家系进行现场调查，并分析其遗传模式。采集每位家系成员外周血标本，提取全基因组DNA。运用聚合酶链式反应(PCR)扩增早老素1(PSEN1)、单过性跨膜蛋白(NCSTN)和早老素增强子2(PSENEN)的所有外显子，经测序与比对后鉴定致病基因突变位点和突变方式。结果：该家系共有3代14人，其中6人患病（男4例，女2例）。对4位现存患者的临床特征进行比较分析表明患者临床表型差异显著。该家系符合常染色体显性遗传模式。对3个上述基因的DNA测序分析发现NCSTN基因第6号外显子存在c.647AC(p.216QP)错义突变，，且在该家系中基因型与表型呈完全共分离现象。同时检测100名正常对照者而未发现该突变。查询美国国家生物技术信息中心（NCBI）网站单核苷酸多态性(SNP)数据库亦未发现该突变。结论：该家系存在一个新的错义突变，即NCSTN基因第6号外显子c.647AC。这可能是该家系患者发病的分子基础。
[Abstract]:Objective: to study the clinical characteristics of a family with reverse acne and the mutation type of its pathogenic gene. Methods: according to the proband diagnosed in outpatient clinic, we traced back to a family of three generations of reverse acne, then investigated the family on the spot and analyzed its genetic pattern. The peripheral blood samples of each family member were collected. The whole genome DNAs were extracted and amplified by polymerase chain reaction (PCR). All exons of the exons of presenin 1 PSEN1, single transmembrane protein (NCSTN) and early age enhancer 2PSENEN) were amplified. The mutation sites and mutation patterns of the pathogenicity gene were identified by sequencing and comparison. Results: in this family, there were 14 persons in 3 generations, 6 of whom were ill (4 males, 4 males). A comparative analysis of the clinical characteristics of 4 extant patients showed that the clinical phenotypic differences were significant. The pedigree was in accordance with the autosomal dominant genetic pattern. The NCSTN gene was found by DNA sequencing analysis of the three genes mentioned above. Exon 6 had a missense mutation of c. 647 ACP p. 216QP, Genotypes and phenotypes were completely cosegregated in the pedigree, and the mutation was not found in 100 normal controls. The single nucleotide polymorphisms (SNPs) database of the National Center for Biotechnology Information (NCBI) website was also not found. Conclusion: there is a new missense mutation in this pedigree, I. e., exon 6 of NCSTN gene c. 647AC. this may be the molecular basis of the disease in this pedigree.
【学位授予单位】：华中科技大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R758.73

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