本文選題：卡爾曼綜合征（KS） + 特發(fā)性低促性腺激素性性腺功能減退癥(IHH)　； 參考：《中國(guó)人民解放軍醫(yī)學(xué)院》2013年碩士論文

【摘要】：目的： 卡爾曼綜合征(Kallmann Syndrome, KS)是特發(fā)性低促性腺激素性性腺功能減退癥（Idiopathic hypogonadotropic hypogonadism，IHH）的一個(gè)獨(dú)特生物模型，即有發(fā)育障礙，又有嗅覺(jué)異常。KS病因分自發(fā)性和遺傳性。為進(jìn)一步明確KS的基因突變及基因突變與臨床表型的關(guān)系，本文研究了7個(gè)KS家系，并與散發(fā)KS及正常人對(duì)照。 方法： 研究7個(gè)KS家系，觀察患者第二性征發(fā)育情況、嗅覺(jué)表型及其他臨床表型；并對(duì)7個(gè)家系先證者分別行目前已知的除CHD7之外的所有KS或嗅覺(jué)正常的IHH(nIHH)相關(guān)基因（19個(gè)）（KAL-1、FGFR1、FGF8、PROKR2、PROK2、NELF、WDR11、HS6ST1、KISS1R、KISS1、TAC3、TACR3、LEPR、LEP、PCSK1、GNRHR、GNRH1、SEMA3A、NDN）外顯子及外顯子、內(nèi)含子交接區(qū)域測(cè)序，并應(yīng)用70例散發(fā)KS及200例健康中國(guó)人做對(duì)照。 結(jié)果： 家系1、2、7第二性征發(fā)育差、嗅覺(jué)重度或完全喪失；家系3、4、5、6第二性征和嗅覺(jué)癥狀輕重不一，并且有可逆性KS病例，呈現(xiàn)明顯不完全外顯性。7個(gè)家系中有5個(gè)家系檢測(cè)出基因突變：KAL-1:p.R191ter純和突變（家系1）；KAL-1:p.C13ter純和突變（家系2）;FGFR1：p.R250W雜合突變（家系3）； PROKR2：p.Y113H純和突變（家系4及家系5）。其中KAL-1:p.C13ter尚無(wú)文獻(xiàn)報(bào)道，，是本文發(fā)現(xiàn)的新的突變位點(diǎn)。家系6及家系7未檢測(cè)出任何基因變化。70例散發(fā)KS檢測(cè)上述5個(gè)突變位點(diǎn)，發(fā)現(xiàn)PROKR2：p.Y113H的1個(gè)純和突變和1個(gè)雜合突變，其余位點(diǎn)正常。200例正常對(duì)照中發(fā)現(xiàn)2個(gè)PROKR2：p.Y113H雜合突變，其余位點(diǎn)正常。 結(jié)論： 1.7個(gè)家系中有5個(gè)家系檢測(cè)出基因突變，其中發(fā)現(xiàn)KAL-1的一個(gè)新突變位點(diǎn):c.C39A，p.C13ter。2.KS基因型及表型-基因型關(guān)系均十分復(fù)雜，有的遵循經(jīng)典的單基因遺傳模式，并可以受Lyon假說(shuō)、延遲顯性作用及微缺失影響。有的無(wú)法用單基因遺傳模式解釋?zhuān)赡茏裱蚧蚬鸦蜻z傳（可能有目前尚未發(fā)現(xiàn)的KS/nIHH相關(guān)基因參與），并受環(huán)境和表觀遺傳學(xué)因素影響。
[Abstract]:Objective: Kallmann Synmedrom (KSs) is a unique biological model of idiopathic hypogonadism hypogonadotropic hypogonadismHH. In order to further clarify the relationship between KS gene mutation and clinical phenotype, 7 KS families were studied and compared with sporadic KS and normal controls. Methods: Seven KS families were studied to observe the development of secondary sexual characteristics, olfactory phenotype and other clinical phenotypes. The exons and exons of all known KS or normal olfactory IHHnIHH genes (19 KKL-1FGFR1FGFR1 FGF8PROKR2FGF8PROKR2FGFR2FGF8PROKR2FGFR2FGF8PROKR2FGF8PROKR2FGFR2FGF8PROKR2FGFR2FGF8PROKR2FGFR2FGF8PROKR2FGFR2FGF8PROKR2FGFR2FGFR2FGF8PROKR2FGFR2FGF8PROKR2FGFR2FGF-8PROKR2FGFR2FGF8PROKR2FGF8PROKR2FGFR2FGF8PROKR2MAN HS6ST1KISS1KISS1TAC3CR3KISS1TAC3RACR3LEPREP PCSK1GNRHR-RH1@@ Results: The second sexual sign of 1 family was poor, the second sex sign was severe or lost completely, and the second sex sign and olfactory symptom were different in 3 families, and there were reversible KS cases. In 5 of the 7 families, the gene mutation: KAL-1: p.R191ter homologous and mutated (family 1: KAL-1: p.C13ter) and mutation (family 2FGFR1: p.R250W heterozygosity) were detected in 5 of the 7 families (family 3; PROKR2:p.Y113H homozygosity and mutation (family 4 and family 5). Among them, KAL-1:p.C13ter has not been reported in literature, and it is a new mutation site found in this paper. No gene changes were detected in families 6 and 7. 70 sporadic KS loci were detected. One pure mutation and one heterozygous mutation were found in PROKR2:p.Y113H, and 2 PROKR2:p.Y113H heterozygosity mutations were found in the other normal controls. The other sites are normal. Conclusion: 1. Gene mutations were detected in 5 of the seven families. One of the new mutation sites of KAL-1 was found to be the complex relationship between genotype and phenotypic relationship of KAL-1. Some of them follow the classical single gene genetic model and can be hypothesized by Lyon. Delayed dominance and microdeletion. Some of them can not be explained by single gene genetic model and may follow two genes or oligogenes (there may be genes related to KS/nIHH that have not been found at present and may be affected by environmental and epigenetic factors).
【學(xué)位授予單位】：中國(guó)人民解放軍醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2013
【分類(lèi)號(hào)】：R588;R3416

【共引文獻(xiàn)】

相關(guān)博士學(xué)位論文 前3條

1 法塞;特發(fā)性低促性腺激素性腺功能減退癥及嚴(yán)重性腺功能減退的中國(guó)患者GnRHR基因分子缺陷[D];華中科技大學(xué);2013年

2 茅江峰;不同基因突變對(duì)特發(fā)性低促性腺激素性性腺功能減退癥患者的臨床特點(diǎn)、隱睪和生精療效的影響[D];北京協(xié)和醫(yī)學(xué)院;2013年

3 法塞（Aws Khalid Fathi）;特發(fā)性低促性腺激素性腺功能減退癥及嚴(yán)重性腺功能減退的中國(guó)患者GnRHR基因分子缺陷[D];華中科技大學(xué);2013年

相關(guān)碩士學(xué)位論文 前3條

1 劉冠樓;第二性征發(fā)育不良青少年的細(xì)胞及分子遺傳學(xué)分析[D];華中科技大學(xué);2009年

2 岳巍巍;Kallmann綜合癥的臨床診斷與治療分析[D];廣州醫(yī)學(xué)院;2011年

3 夏開(kāi)德;酵母雙雜交篩選PKR2相互作用蛋白[D];中南大學(xué);2013年

本文編號(hào)：1908565