Research and Development Unit, Human Genetics Department, National Institute of Health Doutor Ricardo Jorge, 4000-055 Porto, Portugal.
Neonatal Screening, Metabolism and Genetics Unit, Human Genetics Department, National Institute of Health Doutor Ricardo Jorge, 4000-055 Porto, Portugal.
Genes (Basel). 2023 Jul 27;14(8):1536. doi: 10.3390/genes14081536.
Mitochondrial diseases are the most common inherited inborn error of metabolism resulting in deficient ATP generation, due to failure in homeostasis and proper bioenergetics. The most frequent mitochondrial disease manifestation in children is Leigh syndrome (LS), encompassing clinical, neuroradiological, biochemical, and molecular features. It typically affects infants but occurs anytime in life. Considering recent updates, LS clinical presentation has been stretched, and is now named LS spectrum (LSS), including classical LS and Leigh-like presentations. Apart from clinical diagnosis challenges, the molecular characterization also progressed from Sanger techniques to NGS (next-generation sequencing), encompassing analysis of nuclear (nDNA) and mitochondrial DNA (mtDNA). This upgrade resumed steps and favored diagnosis. Hereby, our paper presents molecular and clinical data on a Portuguese cohort of 40 positive cases of LSS. A total of 28 patients presented mutation in mtDNA and 12 in nDNA, with novel mutations identified in a heterogeneous group of genes. The present results contribute to the better knowledge of the molecular basis of LS and expand the clinical spectrum associated with this syndrome.
线粒体疾病是最常见的遗传性代谢缺陷疾病，导致三磷酸腺苷生成不足，这是由于体内平衡和适当的生物能量发生故障。儿童中最常见的线粒体疾病表现是 Leigh 综合征（LS），包括临床、神经影像学、生化和分子特征。它通常影响婴儿，但也可能在任何年龄段发生。考虑到最近的更新，LS 的临床表现已经扩展，现在被命名为 LS 谱（LSS），包括经典 LS 和 Leigh 样表现。除了临床诊断的挑战外，分子特征分析也从 Sanger 技术进展到 NGS（下一代测序），包括核（nDNA）和线粒体 DNA（mtDNA）的分析。这种升级恢复了步骤并促进了诊断。因此，我们的论文介绍了葡萄牙 LSS 阳性病例 40 例的分子和临床数据。共有 28 例患者的 mtDNA 发生突变，12 例患者的 nDNA 发生突变，在一组异质基因中发现了新的突变。目前的结果有助于更好地了解 LS 的分子基础，并扩大与该综合征相关的临床谱。
