Department of Medicine, Epilepsy Research Centre, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
Research Institute of the McGill University Medical Centre, Montreal, QC, Canada.
Epilepsia. 2021 Jan;62(1):e22-e28. doi: 10.1111/epi.16766. Epub 2020 Nov 18.
Ring chromosomes occur when the ends of normally rod-shaped chromosomes fuse. In ring chromosome 20 (ring 20), intellectual disability and epilepsy are usually present, even if there is no deleted coding material; the mechanism by which individuals with complete ring chromosomes develop seizures and other phenotypic abnormalities is not understood. We investigated altered gene transcription as a contributing factor by performing RNA-sequencing (RNA-seq) analysis on blood from seven patients with ring 20, and 11 first-degree relatives (all parents). Geographic analysis did not identify altered expression in peritelomeric or other specific chromosome 20 regions. RNA-seq analysis revealed 97 genes potentially differentially expressed in ring 20 patients. These included one epilepsy gene, NPRL3, but this finding was not confirmed on reverse transcription Droplet Digital polymerase chain reaction analysis. Molecular studies of structural chromosomal anomalies such as ring chromosome are challenging and often difficult to interpret because many patients are mosaic, and there may be genome-wide chromosomal instability affecting gene expression. Our findings nevertheless suggest that peritelomeric altered transcription is not the likely pathogenic mechanism in ring 20. Underlying genetic mechanisms are likely complex and may involve differential expression of many genes, the majority of which may not be located on chromosome 20.
当正常的杆状染色体的末端融合时，就会出现环状染色体。在 20 号环状染色体（ring 20）中，即使没有缺失的编码物质，智力残疾和癫痫通常也会存在；患有完全环状染色体的个体如何发生癫痫发作和其他表型异常的机制尚不清楚。我们通过对来自七个患有 ring 20 的患者和 11 个一级亲属（均为父母）的血液进行 RNA 测序（RNA-seq）分析，研究了改变的基因转录作为一个促成因素。地理分析未在端粒周围或其他特定的 20 号染色体区域发现表达改变。RNA-seq 分析显示，在 ring 20 患者中，有 97 个基因可能存在差异表达。其中包括一个癫痫基因 NPRL3，但在反转录 Droplet Digital 聚合酶链反应分析中未得到证实。对环状染色体等结构性染色体异常的分子研究具有挑战性，并且通常难以解释，因为许多患者是镶嵌的，并且可能存在影响基因表达的全基因组染色体不稳定性。然而，我们的研究结果表明，端粒周围改变的转录可能不是 ring 20 的致病机制。潜在的遗传机制可能很复杂，可能涉及许多基因的差异表达，其中大多数基因可能不在 20 号染色体上。
