标题：The m.3290T > C variant might be a protective factor against the pathogenic m.3243 A > G variant: a case study

中文标题：m.3290T＞C 变异可能是针对致病性 m.3243 A＞G 变异的保护因素：一例病例研究

引用信息：Zhang N, Zhang Z, Zhang Y, Su X, Gao Y, Yang J, Zou W, Cao Y, Ji D. The m.3290T > C variant might be a protective factor against the pathogenic m.3243 A > G variant: a case study. Orphanet J Rare Dis. 2025 Jun 13;20(1):306. doi: 10.1186/s13023-025-03774-5. Erratum in: Orphanet J Rare Dis. 2025 Jul 1;20(1):320. doi: 10.1186/s13023-025-03872-4. PMID: 40514671; PMCID: PMC12166622.

摘要：The mitochondrial m.3243 A > G variant is a prevalent mitochondrial disease mutation that causes multisystem maternal inheritance disorders. While clinical severity typically correlates with mutation load, symptom manifestation may be influenced by other variants and environmental factors. Notably, the m.3290T > C variant has been hypothesized as a potential protective variant for m.3243 A > G pathogenicity, though clinical evidence remains limited. Here we reported a six-generation Chinese pedigree carrying both m.3243 A > G and homoplasmic m.3290T > C variants. Clinical and genetic analyses revealed that carriers with extremely high m.3243 A > G heteroplasmy (> 95%) exhibited severe symptoms, whereas those with moderate or high levels showed limited or no clinical symptoms. Our findings provide novel evidence for the protective role of m.3290T > C in mitigating m.3243 A > G pathogenicity, highlighting its potential clinical significance.

中文摘要：线粒体m.3243 A＞G变异是一种常见的线粒体疾病突变，可导致多系统母系遗传性疾病。虽然临床严重程度通常与突变负荷相关，但症状表现可能受其他变异和环境因素的影响。值得注意的是，m.3290T＞C变异被假设为可能对m.3243 A＞G致病性具有保护作用的变异，不过临床证据仍然有限。在此，我们报道了一个同时携带m.3243 A＞G和纯质性m.3290T＞C变异的中国六代家系。临床和遗传学分析显示，m.3243 A＞G异质性极高（＞95%）的携带者表现出严重症状，而中等或较高水平异质性的携带者则症状轻微或无临床症状。我们的研究结果为m.3290T＞C在减轻m.3243 A＞G致病性方面的保护作用提供了新证据，并强调了其潜在的临床意义。

原文链接：https://link.springer.com/article/10.1186/s13023-025-03774-5