联合应用多种遗传学技术诊断性染色体畸变导致的性发育异常

发布时间：2018-03-12 11:14

本文选题：性发育异常　切入点：核型　出处：《中南大学》2012年硕士论文　论文类型：学位论文

【摘要】：背景：性发育异常(Disorders of sex development, DSD),又称为性分化异常(Disorders of sex differentiation),是指先天性的遗传性别、性腺性别、表型性别三者不典型,出现内在性状或外在性状的异常。该病具有表现度的显著差异性及高度遗传异质性,是一系列严重危害人类身心健康的难以归类、难以诊断的复杂性遗传病。而由性染色体数目异常和结构畸变所导致的性发育异常是其中最常见原因,该病简称性染色体DSD,包括45,X Turner综合征(嵌合体,等臂X,环状X等)、47,XXY Klinefelter综合征(48,XXXY,嵌合体等)、45,X/46,XY(混合性腺发育不全,卵睾DSD)和46,XX/46,XY(异源嵌合体,卵睾DSD)。由于性染色体DSD核型的多样性,出现了不同患者表型的差异性,虽大部分依靠传统的细胞遗传学技术能够诊断,但单一技术应用在性染色体DSD患者的诊断存在一定的局限性。目的：探讨多种遗传学技术在性染色体DSD患者诊断中的应用价值,分析性染色体DSD发病的遗传学机制,为该类患者遗传咨询和临床治疗提供依据。方法：联合应用外周血高分辨G显带和C显带核型分析、皮肤成纤维细胞染色体核型分析、SRY基因检测、AZF微缺失检测、中期染色体荧光原位杂交等遗传学技术对22例性发育异常患者进行诊断。结果：22例性发育异常患者中,21例明确诊断为性染色体DSD,其中2例通过皮肤成纤维细胞染色体明确诊断；2例通过FISH技术准确鉴定了微小额外标记染色体的来源；1例混合性腺发育不全患者AZFb区和AZFc区缺失。同时排除了1例被误诊的非性染色体DSD。结论：细胞遗传学、分子遗传学、分子细胞遗传学技术联合应用可提高性染色体DSD诊断的精准性,明确的诊断可为该类患者遗传咨询和临床治疗提供决策依据。
[Abstract]:Background: dysplasia (Disorders of sex development, DSD), also known as abnormal sexual differentiation (Disorders of sex differentiation), refers to the genetic sex, congenital gonadal sex, sex phenotype three atypical abnormal intrinsic or extrinsic character traits. The disease has significant difference degree and a high degree of genetic heterogeneity, is a series of serious harm to human health is difficult to categorize, the complexity of genetic disease is difficult to diagnose. The abnormal sex chromosome number and structure distortion caused by the abnormal sexual development is one of the most common cause of the disease, referred to as sex chromosome DSD, including X 45, Turner syndrome (chimera, etc. arm X, circular X, 47, XXY) and Klinefelter syndrome (48, XXXY, 45, mosaicism), X/46, XY (mixed gonadal dysgenesis, Ovotesticular DSD) and 46 (XY, XX/46, chimera, Ovotesticular DSD). Due to the diversity of chromosome karyotype of DSD There are different phenotypes in different patients. Although most of them can be diagnosed by traditional cytogenetic technology, there are some limitations in the diagnosis of sex chromosome DSD by single technology.
Objective: To explore the application value of multiple genetic techniques in the diagnosis of sex chromosome DSD patients, analyze the genetic mechanism of DSD, and provide evidence for genetic counseling and clinical treatment of these patients.
Methods: combined with peripheral blood high resolution G banding and C banding karyotype analysis, skin fibroblast chromosome karyotype analysis, SRY gene detection, AZF microdeletion detection, metaphase chromosome fluorescence in situ hybridization and other genetic techniques were used to diagnose 22 cases of sexual dysplasia.
Results: 22 cases of patients with sexual abnormality, 21 cases were diagnosed as sex chromosome DSD, including 2 cases by Karytype analysis of skin fibroblasts; 2 cases by FISH accurately identified the source of small supernumerary marker chromosome; 1 cases of mixed gonadal dysgenesis patients in AZFb and AZFc regions and eliminate missing. Non sex chromosome DSD. 1 cases misdiagnosed
Conclusion: the combination of cytogenetics, molecular genetics and molecular cytogenetics can improve the accuracy of DSD diagnosis of sex chromosomes, and the diagnosis can provide a basis for genetic counseling and clinical treatment of such patients.

【学位授予单位】：中南大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R394

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