Human Genetics Program, Department of Pediatrics, New York University School of Medicine, New York, New York 10016, USA.
Am J Med Genet A. 2010 Feb;152A(2):422-6. doi: 10.1002/ajmg.a.33201.
Individuals with rare cytogenetic variants have contributed to our understanding of the genetics of sex development and its disorders. Here, we report on a child with a de novo 12;17 translocation, 46,XX,t(12;17)(q14.3;q24.3) chromosome complement, resulting in SRY-negative 46,XX testicular disorder of sex development (46,XX DSD without campomelic dysplasia). The chromosome 12 breakpoint was mapped via array comparative genomic hybridization (aCGH) of a hybrid somatic cell line to 64.2-64.6 Mb (from the p arm telomere). The chromosome 17 breakpoint was mapped to 66.4-67.1 Mb, that is, upstream of SOX9. The location of the chromosome 17 breakpoint was refined by fluorescence in situ hybridization (FISH) at > or =776 kb upstream of SOX9. Thus, the 12;17 translocation removed part of the SOX9 cis-regulatory region and replaced it with a regulatory element from pseudogene LOC204010 or the next gene, Deynar, of chromosome 12, potentially causing up-regulation of the testis-determining SOX9 gene during gonadal development and the phenotype of 46,XX testicular DSD.
个体的罕见细胞遗传学变异有助于我们理解性别发育及其障碍的遗传学。在这里，我们报告了一例患有新发 12;17 易位的患儿，其染色体核型为 46,XX，t(12;17)(q14.3;q24.3)，导致 SRY 阴性 46,XX 睾丸性发育障碍（46,XX DSD 不伴 Camptomelic 发育不良）。通过杂交体细胞系的比较基因组杂交（aCGH）对 12 号染色体断裂点进行了定位，位于 64.2-64.6 Mb（从 p 臂端粒）。17 号染色体断裂点被定位到 66.4-67.1 Mb，即 Sox9 上游。通过荧光原位杂交（FISH）在 Sox9 上游 >或=776 kb 处对 17 号染色体断裂点进行了精确定位。因此，12;17 易位切除了 Sox9 顺式调控区的一部分，并将其替换为来自假基因 LOC204010 或 12 号染色体上的下一个基因 Deynar 的调控元件，可能导致睾丸决定基因 Sox9 的表达上调，从而导致 46,XX 睾丸性发育障碍的表型。
