一哈萨克族毛囊角化病家系临床特点及ATP2A2基因突变分析研究

发布时间：2018-04-22 21:36

本文选题：毛囊角化病 + DNA突变分析　；参考：《新疆医科大学》2017年硕士论文

【摘要】：目的分析一个哈萨克族毛囊角化病四代49人大家系的临床特点和遗传学特征,检测家系中患者ATP2A2基因的突变位点,分析疾病临床特点和遗传学特征。方法(1)收集此毛囊角化病家系的临床病例资料及家系图谱;(2)提取家系中11例患者外周血样的DNA,并提取家系中33例健康者和100例无亲缘关系的正常人DNA作为对照;(3)针对ATP2A2基因的共21对外显子及外显子和内含子交界处聚合酶链式反应扩增(PCR),最终采用直接测序法对毛囊角化病患者、家系内非患者及正常对照个体的DNA进行检测,并进行基因突变筛查。结果(1)该家系遗传方式属于常染色体显性遗传。(2)通过对ATP2A2基因突变检测,发现该家系中11例患者ATP2A2基因的编码序列显示外显子11的剪切位点发生杂合突变(1288-1G→A),即第1288-1位碱基由G转化为A,而家系中33例正常人和家系外100例正常人检测均未发现该突变,此突变未有文献报道,为新发突变。结论该家系毛囊角化病发病可能是由ATP2A2基因12号外显子的剪切位点发生杂合突变(1288-1G→A)所致,可能是导致该家系临床病变的主要原因,其基因突变也可能与临床严重程度有关。该研究进一步丰富了角化性皮肤遗传病基因型-表型的数据库,为哈萨克族毛囊角化病的发病机制研究、产前遗传咨询、基因诊断及基因治疗。
[Abstract]:Objective to analyze the clinical and genetic characteristics of a family of 49 Kazak people with hair follicular keratosis, to detect the mutation site of ATP2A2 gene, and to analyze the clinical and genetic characteristics of the disease. Methods 1) the clinical data and family map of this family with keratosis were collected. The peripheral blood samples of 11 patients were extracted from the family, and 33 healthy people and 100 unrelated normal persons were extracted from the family as control group. A total of 21 pairs of exons of ATP2A2 gene were amplified by polymerase chain reaction at the junction of exons and introns. The DNA of non-patient and normal individuals were detected and gene mutation was screened. Results 1) the genetic pattern of this family belongs to autosomal dominant inheritance. (2) the mutation of ATP2A2 gene was detected. It was found that the coding sequence of ATP2A2 gene in 11 patients in this pedigree showed a heterozygous mutation at the shear site of exon 11, that is, the 1288-1 base was transformed from G to A, while 33 healthy people and 100 healthy people outside the family were detected. None of the mutations were found, This mutation, which has not been reported in literature, is a new mutation. Conclusion the pathogenesis of hair follicular keratosis in this family may be caused by the heterozygous mutation (1288-1G) in the exon 12 of ATP2A2 gene, which may be the main cause of clinical lesions in this family, and the gene mutation may also be related to the severity of the disease. This study further enriches the genotypic phenotypic database of keratinizing skin hereditary disease, which is useful for the study of pathogenesis, prenatal genetic counseling, gene diagnosis and gene therapy of hair follicular keratosis in Kazak nationality.
【学位授予单位】：新疆医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R758.5

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