女性表型46,XY性发育障碍的临床、病理特征及遗传学检测The clinical features and genetic testing of 3 female 46,XY DSD cases
吴维青;谢建生;张丽;张雁瑞;覃春容;李素丽;陈武斌;周庆华;
摘要(Abstract)：
目的:总结女性表型的46,XY性发育障碍患者的临床及病理学特点,对其进行鉴别诊断及遗传学检测,为类似病例的诊断和鉴别诊断提供借鉴资料。方法:回顾分析2010年至2015年在深圳市妇幼保健院行妇科手术的3例46,XY性发育障碍患者的临床资料。将切除的性腺组织进行病理学诊断;提取患者及家属基因组DNA,应用Sanger测序、二代测序方法、MLPA、染色体基因组芯片分析等方法进行遗传学检测以寻找致病基因变异。结果:1例患者为完全型雄激素不敏感综合征(CAIS),病理结果证实一侧隐睾见精原细胞瘤,其AR基因第7外显子检测到移码突变c.2546_2547 insA(p.N849K,fs X32),此突变为已报道导致CAIS的突变方式;1例患者临床诊断为单纯性腺发育不良,性腺病理结果为不成熟的卵巢组织,患者SRY基因的HMG区域检测到c.206T>C(p.V69A)突变,此突变未见报道;1例患者临床诊断为单纯性腺发育不良,病理结果为双侧性腺母细胞瘤伴无性细胞瘤,性发育相关基因未检测到明确的致病突变。结论:综合利用多种检测方法对女性表型46,XY性发育障碍患者进行致病基因检测,其中2例患者分别由AR基因、SRY基因突变引起,其中SRY基因c.206T>C(p.V69A)为新发现的突变。
关键词(KeyWords)： 性发育障碍;雄激素不敏感综合征;单纯性腺发育不良;雄激素受体基因;SRY基因;生殖细胞肿瘤
基金项目(Foundation): 深圳市科技计划项目(No:JCYJ20150402090413001);; 国家自然青年基金项目(No:81601299)
作者(Authors): 吴维青;谢建生;张丽;张雁瑞;覃春容;李素丽;陈武斌;周庆华;
DOI: 10.13283/j.cnki.xdfckjz.2017.09.006
参考文献(References)：
- [1]Hughes IA,Houk C,Ahmed SF,et al.LWPES Consensus Group.ESPE Consensus Group.Consensus statement on management of intersex disorders[J].Arch Dis Child,2006,91(7):554-563
- [2]Brinkmann AO,Jenster G,Ris-Stalpers C,et al.Androgen receptor mutations[J].J Steroid Biochem Mol Biol,1995,53(1-6):443-448
- [3]Ahmed SF,Cheng A,Dovey L,et al.Phenotypic features,androgen receptor binding,and mutational analysis in 278clinical cases reported as androgen insensitivity syndrome[J].J Clin Endocrinol Metab,2000,85(2):658-665
- [4]King TF,Conway GS.Swyer syndrome[J].Curr Opin Endocrinol Diabetes Obes,2014,21(6):504-510
- [5]吴维青,刘洋,耿茜,等.完全型雄激素不敏感综合征一个家系的产前遗传学诊断[J].中华医学杂志,2016,96(47):3793-3796
- [6]Scherer G,Held M,Erdel M,et al.Three novel SRY mutations in XY gonadal dysgenesis and the enigma of XY gonadal dysgenesis cases without SRY mutations[J].Cytogenet Cell Genet,1998,80(1-4):188-192
- [7]Racca JD,Chen YS,Maloy JD,et al.Structure-function relationships in human testis-determining factor SRY:an aromatic buttress underlies the specific DNA-bending surface of a high mobility group(HMG)box[J].J Biol Chem,2014,89(47):32410-32429
- [8]Tobias ES,Mc Elreavey K.Next generation sequencing for disorders of sex development[J].Endocr Dev,2014,27(1):53-62
- [9]Barbaro M,Cicognani A,Balsamo A,et al.Gene dosage imbalances in patients with 46,XY gonadal DSD detected by an in-house-designed synthetic probe set for multiplex ligation-dependent probe amplification analysis[J].Clin Genet,2008,73(5):453-464
- [10]White S,Ohnesorg T,Notini A,et al.Copy number variation in patients with disorders of sex development due to46,XY gonadal dysgenesis[J].PLo S One,2011,6(3):e17793
- [11]Cools M,Drop SL,Wolffenbuttel KP,et al.Germ cell tumors in the intersex gonad:old paths,new directions,moving frontiers[J].Endocr Rev,2006,27(5):468-484
- [12]祁艳卫.先天性性别异常患儿肿瘤风险的研究进展[J].临床小儿外科杂志,2011,10(3):223-225