Two new mutations in the MTATP6 gene associated with Leigh syndrome

Area of Science:

• Genetics
• Molecular Biology
• Neuroscience

Background:

• Leigh syndrome (LS) is a severe early-onset neurodegenerative disorder.
• Mitochondrial dysfunction, particularly affecting ATP synthesis, is implicated in LS pathogenesis.
• The mitochondrial DNA (mtDNA) encoded MTATP6 gene is crucial for ATP synthase function.

Observation:

• Two children with LS and reduced mitochondrial Mg(2+) ATPase activity were analyzed.
• Patient 1 presented a mild, reversible phenotype with a T9185C heteroplasmic mutation in MTATP6.
• Patient 2 exhibited a severe phenotype and a novel T9191C heteroplasmic mutation in MTATP6.

Findings:

• The T9185C mutation in MTATP6, leading to a leucine-to-proline substitution, was found in patient 1 and his asymptomatic mother.
• The novel T9191C mutation in MTATP6, also causing a leucine-to-proline substitution, was identified in patient 2 and appeared de novo.
• Both mutations occurred in highly conserved regions of the MTATP6 gene, affecting critical ATPase subunits.

Implications:

• These findings expand the known spectrum of MTATP6 gene mutations associated with Leigh syndrome.
• The study underscores the significant role of MTATP6 mutations in the molecular etiology of LS.
• Identifying specific mutations can aid in understanding LS variability and potentially inform future diagnostic or therapeutic strategies.