DMRT1单倍体不足导致性发育异常

基础医学与临床 ›› 2016, Vol. 36 ›› Issue (1): 104-106.

DMRT1单倍体不足导致性发育异常

茅江峰¹,王曦²,聂敏³,伍学焱¹

1. 北京协和医院内分泌科
2. 北京协和医院
3. 中国医学科学院北京协和医学院北京协和医院内分泌科卫生部内分泌重点实验室

收稿日期:2015-06-25 修回日期:2015-10-08 出版日期:2016-01-05 发布日期:2015-12-29
通讯作者: 伍学焱 E-mail:wsheyan@vip.sina.com

Disorders of Sexual Development caused by haploinsufficiency of DMRT1 gene

Received:2015-06-25 Revised:2015-10-08 Online:2016-01-05 Published:2015-12-29

摘要/Abstract

摘要： 目的增加对DMRT1基因单倍体不足导致性发育异常的认识，提高性发育异常疾病的诊断水平。方法描述1例染色体为46XY性发育异常患者的临床特点；对患者及其父母的静脉血进行淋巴细胞培养和染色体核型分析；抽取患者外周血，提取基因组DNA，进行微阵列比较基因组杂交技术（aCGH）扫描。结果 1）患者表现为女性外阴，超声未见子宫和卵巢组织；伴随发育延迟和运动迟缓；临床表现符合“9p缺失综合征”； 2）染色体结果：患者母亲46XX，t(7;9)(q35, p24)；父亲46XY；患儿46XY,der(9)t(7;9)(q35,p24)； 3）aCGH扫描结果：患儿第7号染色体长臂部分位置（144741153-159098761）重复，长约14.37Mb；第9号染色体短臂部分（10001-9733061）缺失，长约9.72Mb，缺失部分包含EZH2、MNX1、 DMRT1、 DMRT2、 SHH、SMARCA2、GLDC、VLDLR、DOCK8和GLIS3基因；结论 DMRT1在性腺发育过程中发挥重要作用。母亲染色体发生平衡易位，因无遗传物质丢失，故不导致疾病发生。在产生配体过程中，因DMRT1单倍体剂量不足，导致子代睾丸发育障碍。

关键词: 9染色体, 性发育异常, DMRT1基因, 单倍体剂量不足

Abstract: Objective: To increase the knowledge on disorders of sex development (DSD) caused by DMRT1 haploinsufficiency. Methods: Clinical features in a patient with 46XY DSD were described. Peripheral lymphocytic karyotype was measured in this patient and her parents. Furthermore, array comparative genomic hybridization (aCGH) was done to the patient. Results: (1) Clinical features: the patient presented with female genital, and neither uterus nor ovaries were detected by B ultrasound. Mental and physical development retardation was observed, consisted with the manifestation of 9p deletion syndrome. (2) Karyotype: Her mother was 46XX,t(7;9)(q35,p24); Her father was 46XY; The patient was 46XY, der(9) t(7;9) (q35,p24); (3) aCGH scan: 14.37Mb triplication was fond in the terminal of 7q (144741153-159098761); 9.72Mb deletion was found in the terminal of 9p (10001-9733061), containing the following genes, EZH2, MNX1, DMRT1, DMRT2, SHH, SMARCA2, GLDC, VLDLR, DOCK8 and GLIS3; Conclusions: DMRT1 gene plays an essential role in gonadal development. Haploinsufficiency in this gene may result in testicular dysplasia and DSD.

Key words: Chromosome 9, Disorders of sex development, DMRT1 gene, Haploinsufficiency

茅江峰王曦聂敏伍学焱. DMRT1单倍体不足导致性发育异常[J]. 基础医学与临床, 2016, 36(1): 104-106.