46,XX男性综合征患儿五例的临床特征及基因分析

Analysis of clinical features and related genes variation in five patients with 46, XX male syndrome

目的 探讨46,XX男性综合征的临床特点及分子遗传学特征.方法 回顾性分析2010年8月至2014年8月上海瑞金医院儿科5例46,XX男性综合征患儿的临床及分子遗传学资料.结果 5例患儿社会性别均为男性,分别因矮小、外生殖器畸形或乳房发育就诊,染色体核型均为46,XX,身高均低于正常男性均值;经Y染色体性别决定基因（SRY基因）检测,其中1例SRY基因阳性,自幼矮小,具有正常男性表型,外生殖器无畸形,睾丸功能缺陷,为SRY基因易位至X染色体末端所致.4例SRY基因阴性者中,3例外生殖器畸形伴隐睾,睾丸细胞不同程度发育不良,其中1例SOX9基因上游基因拷贝数增加,1例DHH基因杂合性缺失,另1例尚未发现明确的病因.还有1例SRY基因阴性但外生殖器正常者,因青春期乳房发育就诊,其SOX9基因及其上游基因拷贝数均增加.结论 46,XX男性综合征患儿呈男性表型,可有矮小、外生殖器畸形或乳房发育,染色体为46,XX,性腺为睾丸或（和）卵睾,无子宫.SRY基因易位、SOX9基因及其上游基因拷贝数增加皆可导致46,XX男性综合征的发生,尚有未确定的病因.

Objective To explore the clinical manifestations and molecular features of 46,XX male syndrome.Method The clinical and molecular data of five 46,XX male syndrome cases treated in the Department of Pediatrics of Shanghai Ruijin Hospital form August 2010 to August 2014 were retrospectively analyzed.Result The five patients were all sociopsychologically males and came to hospital respectively for short stature,ambiguous genitalia or gynecomastia.They were all below the normal male’s average height,and their karyotype was all 46,XX.One case in five was verified as sex determining region of Y chromosome （SRY gene） positive revealed no abnormality in their external genitalia.He had short stature since childhood,whose SRY gene fragments were shown by FISH transferred to the ends of X chromosome.Three cases in four were SRY gene negative with ambiguous genitalia of cryptorchidism and testicular dysplasia to different degrees.The copy number variations of SOX9 gene was found in one case,the loss of heterozygosity area in DHH gene of one case.Another SRY gene negative patient who had normal male external genitalia,came to the hospital due to puberty gynecomastia,that of SOX9 gene and its upstream gene both increased.Conclusion The main clinical characteristics of 46,XX male syndrome are male phenotype,46,XX karyotype,gonad of testis or ovotestis and no uterus.In addition,short stature,ambiguous genitalia or gynecomastia can be one reason for hospital visits.SRY gene translocation,SOX9 gene and its upstream gene copy number increase all can lead to 46,XX male syndrome.The cause of some may play an important role in 46,XX male syndrome,but has not yet been determined.