SRY、AR、RSPO1基因与性分化异常的相关研究

发布时间：2018-04-02 23:15

本文选题：SRY基因　切入点：AR基因　出处：《汕头大学》2011年硕士论文

【摘要】：目的：探讨SRY基因在性分化中的作用；AR基因与完全性雄激素不敏感综合征的关系及分子遗传机制；RSPO1基因与46,XX男性性分化异常的关系。方法：以性分化异常者为研究对象，通过对患者的临床表现、激素水平、超声结果等进行分析，筛选出13个复杂病例，结合相关文献回顾，对不同病例进行外周血细胞遗传学及相关的分子遗传学检测，具体方法如下： 1.常规G显带进行细胞染色体核型分析； 2.PCR扩增检测SRY、AR、RSPO1基因； 3.用ABIPRISM 3730DNA测序仪进行SRY、AR、RSPO1基因测序； 4.对手术切除睾丸组织进行HE染色和免疫组化检查。结果： 1．13个病例中，11例社会性别女性，核型为46,XY；2例社会性别男性，核型为46，XX。11例46，XY女性中，1例SRY基因缺失，其余10例SRY基因阳性，且序列分析均未发现突变，其中2例经AR基因检测确诊为完全性雄激素不敏感综合征。 2．2个完全性雄激素不敏感病例的AR基因均发生新的突变，1例外显子1的第749位碱基由C突变为A（CA），另1例外显子3的第72位碱基由A转换为T（AT）。其中1例手术切除的睾丸组织，HE染色曲细精管内充满发育不良的Sertoli细胞，未见生精细胞及精子，，间质内Leydig细胞增生。免疫组化染色发现AR在Sertoli细胞呈中度表达，在管周肌样细胞呈强阳性表达，Leydig细胞多不表达，仅有散在无规则表达。 3．2例46,XX男性患者SRY基因均为阴性，RSPO1基因为阳性，其中1例患者RSPO1基因内含子5发生GC32AT杂合突变。结论： 1.2例完全性雄激素不敏感综合征均由AR基因突变引起，突变导致雄激素受体功能受损或丧失，从而出现相应临床症状。1例睾丸组织学表现和AR蛋白表达异常，也支持上述结论。新突变的发现丰富了人类AR基因突变数据库。 2. SRY基因的缺失导致46,XY女性性反转的发生，说明SRY基因在性别决定中的重要作用。 3.本研究中1例46,XX男性性分化异常是否由RSPO1基因内含子突变引起，尚待进一步研究。
[Abstract]:Objective:To investigate the role of SRY gene in sex differentiation and the relationship between AR gene and complete androgen insensitive syndrome and the relationship between RSPO1 gene and male sex differentiation abnormality.Methods:By analyzing the clinical manifestations, hormone levels and ultrasound results of patients with abnormal sexual differentiation, 13 complicated cases were selected.Peripheral blood cytogenetics and related molecular genetics were detected in different cases by the following methods:1.The karyotype of cell chromosomes was analyzed by routine G-banding.The RSPO1 gene was detected by 2.PCR.3.The RSPO1 gene was sequenced by ABIPRISM 3730DNA sequencer.4.The testicular tissues were resected with HE staining and immunohistochemistry.Results:1. Among the 13 cases, 11 cases were female with sex, 2 cases were male, 1 case was SRY gene deletion, 10 cases were positive for SRY gene, and no mutation was found in sequence analysis.Two of them were diagnosed as complete androgen insensitive syndrome by AR gene test.2. In 2 complete androgen insensitive cases, there was a new mutation in AR gene. The 749th base of exon 1 was mutated from C to Acara A, and the 72nd base of exon 3 was transformed from A to TGATA.In one case, the testicular tissue was stained with Sertoli cells, no spermatogenic cells and spermatozoa were found in the seminiferous tubules, and Leydig cells proliferated in the interstitial cells.Immunohistochemical staining showed that AR was moderately expressed in Sertoli cells, but strongly expressed in pericyclic myoid cells.The SRY gene was negative in 3. 2 male patients (46 脳 XX), and GC32AT heterozygosity was found in 1 patient with RSPO1 gene intron 5.Conclusion:The 1. 2 cases of complete androgen insensitive syndrome were caused by AR gene mutation, which resulted in the damage or loss of androgen receptor function, resulting in the corresponding clinical symptoms of 1. 1 cases of testicular histological manifestations and abnormal expression of AR protein, which also supported the above conclusion.The discovery of new mutations enriches the human AR gene mutation database.2.The deletion of SRY gene leads to the occurrence of 46 XY female sex reversal, which indicates that SRY gene plays an important role in sex determination.3.In this study, whether the abnormal sex differentiation of 46 male patients was caused by intron mutation of RSPO1 gene remains to be further studied.
【学位授予单位】：汕头大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R394

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