Leigh Syndrome Spectrum: A Portuguese Population Cohort in an Evolutionary Genetic Era

Area of Science:

• Biochemistry
• Genetics
• Pediatrics

Background:

• Mitochondrial diseases are common inherited metabolic disorders affecting ATP generation.
• Leigh syndrome (LS) is the most frequent childhood manifestation, with a spectrum (LSS) encompassing classical and Leigh-like presentations.
• Diagnosis is challenging due to varied clinical features and evolving molecular techniques.

Purpose of the Study:

• To present molecular and clinical data from a Portuguese cohort of 40 Leigh syndrome spectrum cases.
• To analyze mutations in both mitochondrial DNA (mtDNA) and nuclear DNA (nDNA).
• To contribute to understanding the genetic basis and expanding the clinical spectrum of LSS.

Main Methods:

• Retrospective analysis of clinical and molecular data from 40 LSS patients.
• Next-generation sequencing (NGS) for comprehensive mtDNA and nDNA mutation analysis.
• Identification and characterization of genetic mutations.

Main Results:

• 28 patients had mutations in mtDNA, and 12 had mutations in nDNA.
• Novel mutations were identified in a diverse range of genes.
• The study confirmed the genetic heterogeneity of LSS.

Conclusions:

• Molecular characterization using NGS has improved LSS diagnosis.
• The findings expand the known genetic variations and clinical spectrum of LSS.
• This study enhances knowledge of the molecular basis of Leigh syndrome spectrum.