三例性别发育异常患者的分子细胞遗传学分析

发布时间：2018-10-30 12:05

【摘要】：人类性别发育包括性别决定和性别分化两个阶段,是由性染色体和常染色体上一系列性别决定和分化基因调控的。Y染色体决定男性性别发育,它的完整性在性别决定中非常重要,多种涉及Y染色体的畸变会造成诸如性别逆转、性腺发育不全等临床表现。由于性染色体结构的特殊性,在染色体配对重组中可能出现结构异常。在Y染色体结构异常的嵌合核型中,以双着丝粒Y染色体为常见,异常Y染色体的结构和分布的不同造成患者在表形上有较大区别。Y染色体上的SRY基因被认为是睾丸决定的关键基因,它在睾丸决定通路中起着核心作用。女性的两条X染色体在个体发育时会发生随机失活,使得大部分X连锁的基因表达量与只含有一条X染色体的男性相同。当X染色体与常染色体发生易位时,由于易位的X染色体片段不发生失活,因而可能会导致患者发生X染色体部分复制,从而出现性别发育异常。本研究通过常规染色体G带、DAPI带、荧光原位杂交及分子生物学等方法对三例性别发育异常患者发病机制进行分析,其结果如下:患者1为2个月婴儿,临床表现有尿道下裂、单侧隐睾,CT检查发现该患儿具有幼小子宫;发现大约58%细胞核型为46,X,idic(Y)(p11.3),而40%细胞核型为45,XO,2%细胞核型为47,XY idic(Y)(p11.3),未发现46,XY核型;对SRY、AZF基因进行PCR扩增和测序,显示正常。患者2为19岁女性,闭经、身材矮小,幼稚型子宫,卵巢区域可见数个原始卵泡,核型为45,X/46,X,dic(Y)(p11.3),约75%细胞核型为45,XO,25%细胞核型为46,X,dic(Y)(p11.3),未发现46,XY和47,XY idic(Y)(p11.3)核型,患者有正常SRY基因。患者3为15岁女性,闭经、第二性征发育不全、幼稚子宫,患者为涉及4条染色体易位的复杂核型46,X,t(3;9)(3p14;9p23); t(X;6)(q21;6q24)。在这些研究结果的基础上,本文对由于性染色体畸变而导致的性别发育异常的机制进行了分析和讨论。
[Abstract]:Human sex development consists of two stages: sex determination and sex differentiation. It is regulated by a series of sex-determining and differentiation genes on sex chromosome and autosomal. Y chromosome determines male sex development. Its integrity is very important in sex determination, and many aberrations involving Y chromosome can cause clinical manifestations such as sex reversal and gonadal dysplasia. Due to the particularity of sex chromosome structure, structural abnormalities may occur in chromosome pairing recombination. In the chimeric karyotypes with abnormal structure of Y chromosome, the double centromere Y chromosome is common. The difference in structure and distribution of abnormal Y chromosome leads to great difference in the appearance of patients. The SRY gene on Y chromosome is considered to be the key gene of testicular decision, which plays a central role in the testicular decision pathway. The random inactivation of two X chromosomes in women during ontogeny makes most X-linked genes express the same amount as men with only one X chromosome. When X chromosome and autosomal translocation occur, the X chromosome segment of the translocation will not be inactivated, which may lead to partial replication of X chromosome in patients, resulting in abnormal sex development. In this study, the pathogenesis of three patients with sexual dysplasia was analyzed by routine chromosome G band, DAPI band, fluorescence in situ hybridization and molecular biology. The results were as follows: patient 1 was a 2-month-old infant with hypospadias clinically. Unilateral cryptorchidism, CT examination found that the child has a small uterus; It was found that about 58% of the nuclear type was 46 (Y) (p11.3), while 40% of the nuclear type was 45 XY idic (Y) (p11.3), and no 46 XY karyotype was found. The SRY,AZF gene was amplified by PCR and sequenced. Patient 2 was a 19-year-old female with amenorrhea, short stature, immature uterus, several primordial follicles in the ovarian region, 45 X / 46 X / c (Y) (p11.3), and about 75% of the nuclear type was 45 girax. 25% of the nuclear types were 46 XD (Y) (p11.3). No 46 XY and 47 XY idic (Y) (p11.3) karyotypes were found, and normal SRY gene was found in the patients. Patient 3 was a 15-year-old female with amenorrhea, secondary sexual dysplasia, infantile uterus, and complicated karyotype 46 XT (3t9) (3p149p23); t (XM6) (q216Q24) involving four chromosomal translocations. On the basis of these results, this paper analyses and discusses the mechanism of sex development abnormality caused by sex chromosome aberration.
【学位授予单位】：华中科技大学
【学位级别】：硕士
【学位授予年份】：2009
【分类号】：R394

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