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.

中文翻译：

---

环状染色体 20 患者队列的转录组分析

当正常杆状染色体的末端融合时，就会出现环状染色体。在环状染色体 20（环状 20）中，即使没有缺失的编码材料，通常也存在智力障碍和癫痫；具有完整环状染色体的个体发生癫痫和其他表型异常的机制尚不清楚。我们通过对 7 名环 20 患者和 11 名一级亲属（所有父母）的血液进行 RNA 测序 (RNA-seq) 分析，研究了基因转录改变作为一个促成因素。地理分析未发现周粒或其他特定染色体 20 区域的表达改变。RNA-seq 分析揭示了 20 名患者中 97 个潜在差异表达的基因。其中包括一种癫痫基因 NPRL3，但这一发现并未在逆转录 Droplet Digital 聚合酶链反应分析中得到证实。环状染色体等结构染色体异常的分子研究具有挑战性并且通常难以解释，因为许多患者是嵌合体，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，周端粒改变的转录不是环 20 中可能的致病机制。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，其中大部分可能不在 20 号染色体上。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，周端粒改变的转录不是环 20 中可能的致病机制。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，其中大部分可能不在 20 号染色体上。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，周端粒改变的转录不是环 20 中可能的致病机制。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，其中大部分可能不在 20 号染色体上。