中国汉族人遗传性单纯性头皮少毛症家系CDSN基因突变分析

发布时间：2018-05-20 18:40

本文选题：遗传性少毛症 + 单纯性头皮性少症　；参考：《安徽医科大学》2017年硕士论文

【摘要】：研究背景遗传性少毛症是表现为毛发持续性缺失的单基因遗传性皮肤病,此类疾病具有显著的临床特点和遗传分型。临床表现:患者表现为新生儿时期、婴幼儿时期开始出现毛发的脱落,少数患者表现为青春期时发病。患者的眉毛、睫毛、阴毛、腋毛等均可受累或正常。根据遗传性少毛症的临床特点大致可以分为以下5种类型:1.遗传性单纯性头皮性少毛症;2.遗传性单纯性少毛症;3.Marie Unna型少毛症;4.常染色体显性羊毛状发;5.生长期毛发松动综合征等。随着分子遗传学的发展,这些先天性少毛症的致病基因也都陆续的被报道,而我们此次研究则主要是针对遗传性单纯性头皮性少毛症的致病基因CDSN基因的直接测序,检测CDSN基因的突变位点。研究目的确定遗传性单纯性头皮性少毛症大家系致病的一个新的致病突变,从分子遗传学水平阐述其发病机制,并为以后的遗传咨询,基因诊断,提供理论依据,丰富遗传性少毛症遗传突变谱。实验材料与方法对一例遗传性单纯性头皮性少毛症家系成员进行遗传学调查、实验室检查、临床表现及体征的检查;2.经病人知情允许后拔取患者的病发若干进行电镜扫描分析,采集静脉外周全血样本并提取DNA样本;3.用premier 5.0对既往报道过得CDSN基因进行引物设计;4.采用PCR扩增技术,扩增患者及家族内其他成员的CDSN基因的外显子;5.应用ABI3730XL测序仪进行直接测序,确定有无致病性突变;6.根据突变是否符合家系内遗传规律对测序数据进行分析;7.总结国内外文献报道,探讨突变位点与表型之间的关系。结果该家系患者均表现为青春期时出现头皮油脂分泌增加,头发逐渐脱落、稀疏、细软,长到7cm左右不再生长。阴毛、腋毛,眉毛、睫毛,牙齿、指甲等均未受累。体格检查:神清精神可,身体及智力发育未见异常。病发在肖特基场发射高分辨电镜扫描显示:毛发正常。DNA测序结果显示,家系内所有的患者的均出现一个编码区的插入突变(c.520_521ins G),所有家系内正常患者均未发现该插入突变,(3)基因型与表型之间的相关性研究显示,编码区的插入突变(c.520ins G)导致了下游的框移突变,使后续的氨基酸结构发生改变从而引起表型的改变。结论对一个中国遗传性单纯性头皮性少毛症家系,进行CDSN基因直接测序,测序结果分析,发现一个插入突变c.520_521ins G(P.A174fs)。
[Abstract]:Background hereditary hypotrichoresis is a single gene inherited dermatosis characterized by persistent hair loss, which has significant clinical characteristics and genetic typing. Clinical manifestations: the patients presented as neonatal period, infants began to appear hair loss, a few patients showed puberty onset. The eyebrow, eyelash, pubic hair, armpit hair of the patient can be affected or normal. According to the clinical characteristics of hereditary hypotrichobia can be roughly divided into the following five types: 1. Hereditary simple scalp hypodermia 2. Hereditary simple Hypoderma 3. Marie Unna type Hypoderma 4. Autosomal dominant woolly hair 5. Hair loosening syndrome and so on. With the development of molecular genetics, the pathogenetic genes of congenital hypotrichobia have been reported one after another, and our research is mainly aimed at the direct sequencing of the CDSN gene, which is the pathogenetic gene of hereditary simple scalp hypodermia. The mutation site of CDSN gene was detected. Objective to identify a new pathogenetic mutation of hereditary simple scalp hypotrichobia, and to elucidate its pathogenesis from the level of molecular genetics, and to provide theoretical basis for genetic counseling, gene diagnosis and genetic diagnosis. Rich genetic hypotrichobia genetic mutation spectrum. Materials and methods genetic investigation, laboratory examination, clinical manifestation and physical examination of a family member with hereditary simple scalp hypotrichobia were carried out. With the permission of the patient's knowledge, several cases of the disease were extracted and analyzed by scanning electron microscope. The peripheral venous blood samples were collected and the DNA samples were extracted. The primer design of previously reported CDSN gene was carried out with premier 5.0. PCR amplification technique was used to amplify exon 5 of CDSN gene of patients and other members of the family. Direct sequencing was carried out with ABI3730XL sequencer to determine the pathogenicity of mutagenesis. The sequenced data were analyzed according to whether the mutation was in accordance with the genetic rules within the family. The relationship between mutant loci and phenotypes was discussed in this paper. Results the pedigree patients showed increased scalp fat secretion, hair loss, thinning and soft, and no longer growth of 7cm at puberty. Pubic hair, armpit hair, eyebrows, eyelashes, teeth, nails and so on are not involved. Physical examination: Shenqing mind can, physical and mental development is not abnormal. The disease occurred in Schottky Field Emission High Resolution Electron Microscopy (HREM) scanning showed that the hair was normal. DNA sequencing showed that, The insertion mutation of a coding region was found in all the patients in the pedigree, and the correlation between the genotype and phenotype was not found in normal patients in all families. The insertion mutation of coding region, c. 520ins G), led to the downstream frame shift mutation, resulting in subsequent amino acid structure changes and phenotypic changes. Conclusion the CDSN gene was directly sequenced in a Chinese family with hereditary simple scalp hypotrichobia, and the result of sequencing showed that an insertion mutation c.520_521ins P.A174fsN was found.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R758.71

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