Department of Human and Medical Genetics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, Santariškių Str. 2, Vilnius, LT-08661, Lithuania.
Orphanet J Rare Dis. 2023 Oct 2;18(1):307. doi: 10.1186/s13023-023-02921-0.
Mitochondrial Diseases (MDs) are a diverse group of neurometabolic disorders characterized by impaired mitochondrial oxidative phosphorylation and caused by pathogenic variants in more than 400 genes. The implementation of next-generation sequencing (NGS) technologies helps to increase the understanding of molecular basis and diagnostic yield of these conditions. The purpose of the study was to investigate diagnostic and genotypic spectrum in patients with suspected MD. The comprehensive analysis of mtDNA variants using Sanger sequencing was performed in the group of 83 unrelated individuals with clinically suspected mitochondrial disease. Additionally, targeted next generation sequencing or whole exome sequencing (WES) was performed for 30 patients of the study group.
The overall diagnostic rate was 21.7% for the patients with suspected MD, increasing to 36.7% in the group of patients where NGS methods were applied. Mitochondrial disease was confirmed in 11 patients (13.3%), including few classical mitochondrial syndromes (MELAS, MERRF, Leigh and Kearns-Sayre syndrome) caused by pathogenic mtDNA variants (8.4%) and MDs caused by pathogenic variants in five nDNA genes. Other neuromuscular diseases caused by pathogenic variants in seven nDNA genes, were confirmed in seven patients (23.3%).
The wide spectrum of identified rare mitochondrial or neurodevelopmental diseases proves that MD suspected patients would mostly benefit from an extensive genetic profiling allowing rapid diagnostics and improving the care of these patients.
线粒体疾病（MDs）是一组异质性的神经代谢疾病，其特征为线粒体氧化磷酸化受损，由 400 多个基因的致病性变异引起。下一代测序（NGS）技术的应用有助于提高对这些疾病的分子基础和诊断率的认识。本研究旨在探讨疑诊 MD 患者的诊断和基因型谱。对 83 名临床疑诊线粒体疾病的无亲缘关系个体进行了综合分析 mtDNA 变异的 Sanger 测序。此外，对研究组的 30 名患者进行了靶向下一代测序或全外显子组测序（WES）。
疑诊 MD 患者的总体诊断率为 21.7%，而应用 NGS 方法的患者组则增至 36.7%。11 例（13.3%）患者确诊为线粒体疾病，包括由致病性 mtDNA 变异引起的少数经典线粒体综合征（MELAS、MERRF、Leigh 和 Kearns-Sayre 综合征）（8.4%）和由 5 个 nDNA 基因的致病性变异引起的 MD。另外 7 例（23.3%）患者的致病性变异导致其他神经肌肉疾病。
所鉴定的罕见线粒体或神经发育疾病的广泛谱表明，疑诊 MD 患者大多受益于广泛的遗传分析，从而能够快速诊断，并改善这些患者的护理。
