Modan-Moses Dalit, Litmanovitch Talia, Rienstein Shlomit, Meyerovitch Joseph, Goldman Boleslaw, Aviram-Goldring Ayala
Pediatric Endocrinology Service, Chaim Sheba Medical Center, Tel-Hashomer, Israel.
Am J Med Genet A. 2003 Jan 30;116A(3):300-3. doi: 10.1002/ajmg.a.10869.
Abnormal recombination between the X and Y chromosomes during meiosis, occurring outside the pseudoautosomal region, can result in translocation of the SRY gene from the Y to the X chromosome, and consequently in abnormal sexual differentiation, such as the development of 46,XX males or true hermaphroditism. In this report we present clinical, cytogenetic, and molecular-cytogenetic data of a patient with ambiguous genitalia and true hermaphroditism, who had a unique mosaic karyotype, comprising three different cell lines: 46,XX(SRY+), 45,X(SRY+), and 45,X. The mosaic karyotype of our patient probably represents two different events: abnormal recombination between the X and Y chromosomes during paternal meiosis, and postzygotic loss of one of the X chromosomes. Replication studies demonstrated that in 80% of the XX cells, the SRY sequence was located on the active X chromosome. This finding suggests nonrandom X inactivation and, together with the presence of the SRY gene, explains the male phenotype of our patient. On the other hand, the presence of the 45,X cell line may have contributed to genital ambiguity. We conclude that fluorescence in situ hybridization (FISH) analysis with SRY probes is highly recommended and allows accurate diagnosis and optimal management in cases of 46,XX hermaphroditism and ambiguous genitalia.
减数分裂过程中，X和Y染色体在假常染色体区域之外发生异常重组，可导致SRY基因从Y染色体易位至X染色体，进而导致性分化异常，如46,XX男性或真两性畸形的发生。在本报告中，我们展示了一名生殖器模糊和真两性畸形患者的临床、细胞遗传学和分子细胞遗传学数据，该患者具有独特的嵌合核型，由三种不同的细胞系组成：46,XX(SRY+)、45,X(SRY+)和45,X。我们患者的嵌合核型可能代表两个不同的事件：父本减数分裂期间X和Y染色体之间的异常重组，以及合子后一条X染色体的丢失。复制研究表明，在80%的XX细胞中，SRY序列位于活性X染色体上。这一发现提示了非随机X失活，并且与SRY基因的存在一起，解释了我们患者的男性表型。另一方面，45,X细胞系的存在可能导致了生殖器模糊。我们得出结论，强烈推荐使用SRY探针进行荧光原位杂交（FISH）分析，其可在46,XX两性畸形和生殖器模糊的病例中实现准确诊断和最佳管理。
