六例Y染色体短臂片段易位所致46,XX男性综合征患者的细胞和分子遗传学研究

摘要

Objective To characterize molecular and cytogenetic abnormalities in six 46,XX males,and to investigate the clinical manifestations and underlying mechanisms in such patients.Methods Clinical data of six XX male patients were collected.Karyotyping,multiple polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH) were utilized to detect and locate the sex determining region (SRY) gene.Results PCR and FISH showed that all patients were SRY-positive XX males.All patients have their SRY gene located at the tip of derivative X chromosomes,which have resulted from translocation between short arms of X and Y chromosomes. High resolution karyotyping at 550-750 band level has revealed that the translocation breakpoints were at Xp22.33 and Yp11.2 in three patients.In the remaining patients,the breakpoints were either at Xp22.32 and Yp11.31 or Xp22.31 and Yp11.2.The breakpoints at Xp22.32,Xp22.31 and Yp11.31 were rarely reported.Genotype-phenotype correlation analysis indicated that the clinical manifestations were age-specific.Four adult patients have come to clinical attention due to infertility,with typical features including azoospermia and testis dysgenesis,whereas poorly developed secondary sexual characteristics and short stature were main complaints of adolescence patients,and short stature was the sole symptom in a child patient.Conclusion Combined karyotyping,PCR and FISH are important for the analysis of XX males. Particularly,high resolution karyotyping is valuable for the refinement of chromosome breakpoints and detailed analysis of genotype-phenotype correlation.%目的 明确6例46,XX男性综合征患者细胞遗传和分子遗传水平的异常,探讨X-Y短臂易位所致46,XX男性综合征的临床特点和发病机制.方法 临床收集6例46,XX男性患者的表型数据,采用染色体核型分析、聚合酶链反应、荧光原位杂交对SRY基因进行检测和定位.结果 6例患者均为SRY阳性XX男性,携带一条由包含SRY区域的Y染色体短臂片段易位至X染色体短臂而构成的异常X染色体.3例患者通过550～700条带染色体核型分析确定了X-Y易位的断裂位点,均位于Xp22.33和Yp11.2;另外3例患者推测其断裂点位于Xp22.32和Yp11.31,或是Xp22.31和Yp11.2,其中Xp22.32、Xp22.31和Yp11.31的断裂位点既往报道较少.不同年龄段SRY阳性46,XX男性临床表现各有特点.4例成年男性患者均因不育而就诊,表现为无精及性发育不良;1例青少年患者以身材矮小和第二性征发育不良为主要特征;1例儿童患者以身材矮小为唯一表现.结论 染色体核型分析、聚合酶链反应和荧光原位杂交等方法的综合运用在46,XX男性综合征的诊断中具有重要意义.高分辨染色体核型分析对于易位导致的XX男性综合征的断裂点机制研究,以及基因型表型关联的深入分析有指导作用.