摘要目的 探讨1例46,XY女性性反转患者的遗传发病机制.方法 应用核型分析方法分析外周血淋巴细胞染色体、荧光原位杂交(fluorescence in situ hybridization,FISH)技术确认性染色体、Sanger测序法对SRY基因测序、下一代测序技术对外周血DNA外显子组测序、多重连接依赖探针扩增(multiplex ligation-dependent probe amplification,MLPA)技术检测NR0B1、SF1、SRY、SOX9、WNT4基因拷贝数变异.结果 患者染色体核型为46,XY;FISH分析结果显示性染色体为特异的X和Y信号;Sanger测序未检出SRY基因变异,外显子组高通量测序未见该疾病相关的有害变异,在Xp21上有大约67.31 kb的重复片段,此片段包含MAGEB1、MAGEB3、MAGEB4和NR0B1基因;经MLPA分析结果显示,患者和母亲的NR0B1基因有1个拷贝重复.结论 Xp21携带的NR0B1基因重复引起的46,XY女性性反转,由表型正常的携带者母亲以X连锁隐性遗传方式传递,具有隐匿性和较高发病率的特点.

abstractsObjective To explore the pathogenesis of a 46,XY female with sex reversal.Methods Peripheral blood lymphocytes of the patient were subjected to G-banding karyotype analysis. Sex chromosomes were analyzed with fluorescence in situ hybridization (FISH).SRY gene was analyzed by Sanger sequencing.The whole exome of the patient was subjected to next generation sequencing.Copy number variations (CNVs)of the NR0B1,SF1,SRY,SOX9 and WNT4 genes were validated by multiplex ligation-dependent probe amplification (MLPA).Results The patient had a 46,XY karyotype.FISH analysis showed that her sex chromosomes were X and Y.No mutation was found in the SRY gene,and no pathogenic mutation was detected in her exome.However,a duplication spanning approximately 67.31 kb encompassing the MAGEB1,MAGEB3,MAGEB4 and NR0B1 genes at Xp21,was predicted by software analysis.MLPA confirmed duplication of the NR0B1 gene in the patient and her mother.Conclusion A duplication fragment of Xp21 encompassing the NR0B1 gene in the 46,XY female with sex reversal is transmitted from her asymptomatic carrier mother.Attention should be paid towards the insidious nature and high morbidity of this duplication.