本文選題：SRY基因　切入點(diǎn)：AR基因　出處：《汕頭大學(xué)》2011年碩士論文

【摘要】：目的： 探討SRY基因在性分化中的作用；AR基因與完全性雄激素不敏感綜合征的關(guān)系及分子遺傳機(jī)制；RSPO1基因與46,XX男性性分化異常的關(guān)系。 方法： 以性分化異常者為研究對象，通過對患者的臨床表現(xiàn)、激素水平、超聲結(jié)果等進(jìn)行分析，篩選出13個(gè)復(fù)雜病例，結(jié)合相關(guān)文獻(xiàn)回顧，對不同病例進(jìn)行外周血細(xì)胞遺傳學(xué)及相關(guān)的分子遺傳學(xué)檢測，具體方法如下： 1.常規(guī)G顯帶進(jìn)行細(xì)胞染色體核型分析； 2.PCR擴(kuò)增檢測SRY、AR、RSPO1基因； 3.用ABIPRISM 3730DNA測序儀進(jìn)行SRY、AR、RSPO1基因測序； 4.對手術(shù)切除睪丸組織進(jìn)行HE染色和免疫組化檢查。 結(jié)果： 1．13個(gè)病例中，11例社會(huì)性別女性，核型為46,XY；2例社會(huì)性別男性，核型為46，XX。11例46，XY女性中，1例SRY基因缺失，其余10例SRY基因陽性，且序列分析均未發(fā)現(xiàn)突變，其中2例經(jīng)AR基因檢測確診為完全性雄激素不敏感綜合征。 2．2個(gè)完全性雄激素不敏感病例的AR基因均發(fā)生新的突變，1例外顯子1的第749位堿基由C突變?yōu)锳（CA），另1例外顯子3的第72位堿基由A轉(zhuǎn)換為T（AT）。其中1例手術(shù)切除的睪丸組織，HE染色曲細(xì)精管內(nèi)充滿發(fā)育不良的Sertoli細(xì)胞，未見生精細(xì)胞及精子，，間質(zhì)內(nèi)Leydig細(xì)胞增生。免疫組化染色發(fā)現(xiàn)AR在Sertoli細(xì)胞呈中度表達(dá)，在管周肌樣細(xì)胞呈強(qiáng)陽性表達(dá)，Leydig細(xì)胞多不表達(dá)，僅有散在無規(guī)則表達(dá)。 3．2例46,XX男性患者SRY基因均為陰性，RSPO1基因?yàn)殛栃�，其�?例患者RSPO1基因內(nèi)含子5發(fā)生GC32AT雜合突變。 結(jié)論： 1.2例完全性雄激素不敏感綜合征均由AR基因突變引起，突變導(dǎo)致雄激素受體功能受損或喪失，從而出現(xiàn)相應(yīng)臨床癥狀。1例睪丸組織學(xué)表現(xiàn)和AR蛋白表達(dá)異常，也支持上述結(jié)論。新突變的發(fā)現(xiàn)豐富了人類AR基因突變數(shù)據(jù)庫。 2. SRY基因的缺失導(dǎo)致46,XY女性性反轉(zhuǎn)的發(fā)生，說明SRY基因在性別決定中的重要作用。 3.本研究中1例46,XX男性性分化異常是否由RSPO1基因內(nèi)含子突變引起，尚待進(jìn)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.
【學(xué)位授予單位】：汕頭大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2011
【分類號】：R394

【參考文獻(xiàn)】

相關(guān)期刊論文 前8條

1 遲鋮;母義明;;雄激素不敏感綜合征[J];中國實(shí)用內(nèi)科雜志;2006年20期

2 Yun-Fai Chris Lau;;The human and mouse sex-determining SRY genes repress the Rspo1/β-catenin signaling[J];遺傳學(xué)報(bào);2009年04期

3 ;46,XX male sex reversal syndrome[J];Asian Journal of Andrology;2004年02期

4 蔣三亮;張思仲;楊軍;;性反轉(zhuǎn)綜合征患者的分子病因?qū)W研究[J];中華醫(yī)學(xué)遺傳學(xué)雜志;1993年01期

5 張思仲;性別、SRY基因和性分化異常[J];中華醫(yī)學(xué)遺傳學(xué)雜志;1995年05期

6 劉智，熊正剛，肖廣惠，賴伏英，邱洛琳，陳洪波，朱定爾;七例46，XY女性的SRY基因分析[J];中華醫(yī)學(xué)遺傳學(xué)雜志;1995年05期

7 劉曉翌;付姣;肖曉素;賀蓉;盧麗華;王勇強(qiáng);;性反轉(zhuǎn)綜合征患者SRY、SOX9基因檢測[J];中國優(yōu)生與遺傳雜志;2008年09期

8 付姣;劉曉翌;;SRY、SOX9、DAX-1基因與性反轉(zhuǎn)綜合征的研究進(jìn)展[J];中國優(yōu)生與遺傳雜志;2009年03期

本文編號：1702545