Abstract:

Objective    To analyze clinical characteristics of children with mixed gonadal dysgenesis and ambiguous genitalia and its relationship with the molecular etiology. Methods    A total of 5 children diagnosed with mixed gonadal dysgenesis（MGD） accompanied by ambiguous genitalia between January 2002 and December 2014 in Ruijin Hospital of Shanghai Jiaotong University School of Medicine were enrolled. The detailed medical history，physical examination and laboratory tests had been performed for all children. Genomic DNA from peripheral blood leukocytes was obtained for detecting the existence of Y chromosome microdeletions and copy number variations of genes related to sex development（WNT4，NR5A1，SOX9，Cxorf21） by multiplex ligation-dependent probe amplification（MLPA）. Results    5 patients have diverse clinical phenotypes. 3 of them were raised male while the other 2 were raised female. There were different segments and amounts of Y chromosome microdeletions in 4 MGD patients. No copy number variations of WNT4，NR5A1，SOX9 and Cxorf21 were found. Conclusion    Y chromosome microdeletions show high incidence in the MGD children and it may be one of the molecular etiology of MGD extensive clinical spectrum while there seems no clear association between clinical phenotype and peripheral blood chromosome karyotype.

Key words: mixed gonadal dysgenesis, ambiguous genitalia, clinical analysis, Y chromosome microdeletions, MLPA

摘要：

目的    分析混合性性腺发育不良（mixed gonadal dysgenesis，MGD）伴外生殖器畸形患儿的临床特征及其与分子遗传学的相关性。方法    收集2002年1月至2014年12月因外生殖器畸形就诊于上海交通大学医学院附属瑞金医院儿内科5例患儿病例资料，其染色体为45，X/46，XY嵌合体或包含45，X/46，XY的其他嵌合体。分析其临床特征并进行相关辅助检查，采用多重连接依赖式探针扩增技术（multiplex ligation-dependent probe amplification，MLPA）检测外周血DNA中Y染色体微缺失情况及性发育过程相关基因拷贝数变化。结果    5例MGD患儿临床表型不一，其中3例为男性抚养，2例女性抚养。4例存在不同片段及数量的Y染色体微缺失，5例均未检测到WNT4、NR5A1、SOX9、Cxorf21的拷贝数异常。  结论    MGD临床表型谱广泛，外生殖器畸形严重程度不一。临床表型和外周血染色体核型嵌合比例之间无明显关联。Y染色体微缺失在MGD中的发生率很高，微缺失的范围大小可能和外生殖器的男性化程度正相关。

关键词: 混合性性腺发育不良, 外生殖器畸形, 临床分析, Y染色体微缺失, 多重连续依赖式探针扩增技术