Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
Am J Med Genet A. 2010 Feb;152A(2):373-82. doi: 10.1002/ajmg.a.33219.
Two brothers, with dissimilar clinical features, were each found to have different abnormalities of chromosome 20 by subtelomere fluorescence in situ hybridization (FISH). The proband had deletion of 20p subtelomere and duplication of 20q subtelomere, while his brother was found to have a duplication of 20p subtelomere and deletion of 20q subtelomere. Parental cytogenetic studies were initially thought to be normal, both by G-banding and by subtelomere FISH analysis. Since chromosome 20 is a metacentric chromosome and an inversion was suspected, we used anchored FISH to assist in identifying a possible inversion. This approach employed concomitant hybridization of a FISH probe to the short (p) arm of chromosome 20 with the 20q subtelomere probe. We identified a cytogenetically non-visible, mosaic pericentric inversion of one of the maternal chromosome 20 homologs, providing a mechanistic explanation for the chromosomal abnormalities present in these brothers. Array comparative genomic hybridization (CGH) with both a custom-made BAC and cosmid-based subtelomere specific array (TEL array) and a commercially available SNP-based array confirmed and further characterized these rearrangements, identifying this as the largest pericentric inversion of chromosome 20 described to date. TEL array data indicate that the 20p breakpoint is defined by BAC RP11-978M13, approximately 900 kb from the pter; SNP array data reveal this breakpoint to occur within BAC RP11-978M13. The 20q breakpoint is defined by BAC RP11-93B14, approximately 1.7 Mb from the qter, by TEL array; SNP array data refine this breakpoint to within a gap between BACs on the TEL array (i.e., between RP11-93B14 and proximal BAC RP11-765G16).
两个兄弟，临床特征不同，通过端粒荧光原位杂交（FISH）发现他们的 20 号染色体都有不同的异常。先证者 20p 端粒缺失，20q 端粒重复，而他的兄弟则发现 20p 端粒重复，20q 端粒缺失。父母的细胞遗传学研究最初认为是正常的，无论是 G 带分析还是端粒 FISH 分析。由于 20 号染色体是中央着丝粒染色体，怀疑存在倒位，我们使用锚定 FISH 来协助识别可能的倒位。这种方法采用同时杂交 20 号染色体短臂（p）的 FISH 探针和 20q 端粒探针。我们鉴定出一个细胞遗传学上不可见的、镶嵌性的母源 20 号染色体同源体的中央着丝粒倒位，为这对兄弟中存在的染色体异常提供了机制解释。使用定制的 BAC 和基于 cosmid 的端粒特异性阵列（TEL 阵列）以及商业上可用的 SNP 基阵列的阵列比较基因组杂交（CGH）进一步证实和表征了这些重排，确定这是迄今为止描述的最大的 20 号染色体中央着丝粒倒位。TEL 阵列数据表明 20p 断点由 BAC RP11-978M13 定义，距离 pter 约 900 kb；SNP 阵列数据表明该断点发生在 BAC RP11-978M13 内。20q 断点由 TEL 阵列上的 BAC RP11-93B14 定义，距离 qter 约 1.7 Mb；SNP 阵列数据将该断点细化为 TEL 阵列上 BAC 之间的一个缺口（即，在 BAC RP11-93B14 和近端 BAC RP11-765G16 之间）。
