1 - Research and Development Unit, Human Genetics Department, National Institute of Health Doutor Ricardo
2 - Neonatal Screening, Metabolism and Genetics Unit, Human Genetics Department, National Institute of Health Doutor Ricardo Jorge
3 - Inherited Metabolic Disease Reference Center, Lisbon North University Hospital Center (CHULN), EPE
4 - Inherited Metabolic Disease Reference Center, Pediatric Hospital, Hospital and University Center of Coimbra
5 - Neurogenetics Department, Faculdade de Medicina de São Jose do Rio Preto
6 - Oporto Hospital Centre, University of Porto
7 - Unit for Multidisciplinary Research in Biomedicine, Instituto de Ciências Biomédicas Abel Salazar, Porto
8 - Department of Neurology Porto Hospital and University Centre, EPE
9 - Reference Center for Inherited Metabolic Disorders, University Hospital Centre S. João
10 - Department of Pediatrics, Hospital Centre, EPE, 4434-502 Vila Nova de Gaia, Portugal
11 - Department of Pediatrics, Hospital D. Estefânia, 1169-045 Lisbon, Portugal
- Publicação: Genes 2023, 14(8), 1536; https://doi.org/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 fromSanger techniques toNGS (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.
Palavras Chave: leigh syndrome; mitochondrial disorders; mutational spectrum; clinical spectrum; NGS