DMRT1基因变异/单倍剂量不足与46,XY性发育异常  

DMRT1 gene variant/haploinsufficiency and 46,XY disorders of sex development

作　　者：潘丽丽[1] 苏喆[1] 刘霞[1] 温鹏强[1] 江贤萍[1] 范舒旻[1] 徐万华[1] 李守林[1] Pan Lili;Su Zhe;Liu Xia;Wen Pengqiang;Jiang Xianping;Fan Shumin;Xu Wanhua;Li Shouling(Shenzhen Children′s Hospital DSD Multidisciplinary Team,Shenzhen 518038,China)

机构地区：[1]深圳市儿童医院DSD多学科协作组,518038

出　　处：《中华内分泌代谢杂志》2020年第10期855-860,共6页Chinese Journal of Endocrinology and Metabolism

基　　金：广东省高水平临床重点专科(深圳市配套建设经费)项目(SZGSP012)。

摘　　要：目的分析4例doublesex和mab-3相关转录因子1(doublesex and mab-3 related transcription factor 1,DMRT1)基因变异/单倍剂量不足所致的46,XY性发育异常(46,XY DSD)患儿的临床特征,以提高医生对此病的认识。方法回顾性收集4例46,XY DSD患儿的病史、体格检查、内分泌功能评估、性腺病理及遗传学资料。结果例1为DMRT1基因变异c.332G>T(P.Arg111Met)杂合错义新发变异,因"闭经"于15岁就诊,外生殖器男性化得分(external masculinization scores,EMS)为0分。DMRT1基因单倍剂量不足3例:9p末端依次存在1.2 Mb、5.1 Mb和6.0 Mb片段缺失,其中例3合并5p区域33.3 Mb重复。3例就诊年龄均在1岁以内,社会性别2例为女性,1例为男性,均因"外生殖器外观异常"就诊,EMS依次为1分、0分、5分。例1和例3内分泌评估提示原发性性腺功能减退,性腺病理均为完全性性腺发育不良,例2提示Leydig细胞功能良好、Sertoil细胞功能欠佳,性腺病理为混合性性腺发育不良。例3在18个月龄诊断为性腺母细胞瘤。例4患儿内分泌评估示睾丸功能正常,暂未同意活检。4例染色体核型均为46,XY。结论在DMRT1基因变异/单倍剂量不足的46,XY DSD患者中,前者初诊年龄偏大,后者就诊年龄偏小,性腺功能可表现为从正常到完全性性腺发育不良。此类患者存在性腺母细胞瘤高风险,且发病年龄小,对性腺发育不良者应及早行性腺活检。Objective To summarize the clinical manifestations of four patients with 46,XY disorders of sex development(46,XY DSD)due to doublesex and mab-3 related transcription factor 1(DMRT1)gene variant/haploinsufficiency,and to improve the understanding of clinicians for this disease.Methods The medical history,physical examination,endocrine function assessment,gonadal pathology,and genetic data of 4 patients with 46,XY DSD were retrospectively collected.Results A heterozygous new missense mutation in DMRT1 was found in one child.The chief complain was primary amenorrhoea at the age of 15 years,with the external masculinisation score(EMS)0.The DMRT1 haploinsufficiency was found in 3 cases,1.2 Mb,5.1 Mb,and 6.0 Mb fragments were deleted at the 9p,and one of 3 cases had 33.3 Mb repeats in the 5p.All patients visited doctor under 1 year.Two patients were raised as females,and one was raised as male.All chief complains were external genital abnormalities,EMS of them were 1,0,and 5 respectively.Endocrine evaluation of 2 out of 4 children showed varying degrees of primary hypogonadism,and presented with complete gonadal dysgenesis.One patient showed a well function of Leydig cells and poorly function of Sertoil cells,and presented with mixed gonadal dysgenesis.One of 3 cases was diagnosed with gonadoblastoma at the age of 18 months.Patient No.4 didn′t agree with the gonadal biopsy.The chromosome karyotypes of 4 children were 46,XY.Conclusions The visiting ages of 46,XY DSD patients caused by DMRT1 variation were older than those of patients caused by DMRT1 haploinsufficiency.The clinical manifestations are complex,and gonadal function can vary from normal to complete gonadal dysgenesis.Such patients are at high risk of gonadoblastoma and young onset.Gonadal biopsy should be performed as early as possible.

关 键 词：DMRT1基因 单倍剂量不足 变异 性发育异常 性腺母细胞瘤 

分 类 号：R725.9[医药卫生—儿科]