PDF(Pubmed)
Abstract：
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.
摘要：
线粒体疾病是最常见的遗传性先天性代谢错误，导致ATP生成不足，由于稳态和适当的生物能学的失败。儿童中最常见的线粒体疾病表现是Leigh综合征（LS），包括临床，神经放射学，生物化学，和分子特征。它通常影响婴儿，但在生命中随时发生。考虑到最近的更新，LS的临床表现已经延长，现在被命名为LS频谱(LSS)，包括经典的LS和类似Leigh的演示文稿。除了临床诊断挑战，分子表征也从Sanger技术发展到NGS（下一代测序），包括核（nDNA）和线粒体DNA（mtDNA）的分析。此升级恢复了步骤并有利于诊断。特此,本文介绍了葡萄牙40例LSS阳性病例的分子和临床数据.共有28例患者出现mtDNA突变，12例出现nDNA突变，在一组异质基因中发现了新的突变。本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范围。
