Molecular–Clinical Correlations in a Family with Variable Tissue Mitochondrial DNA T8993G Mutant Load

The study examined a family with the T8993G mitochondrial DNA mutation, which is linked to Leigh syndrome (LS) and neurogenic muscle weakness, ataxia, retinitis pigmentosa (NARP). Two brothers exhibited high mutant loads (>90%) in all tissues, consistent with severe disease. Their sister, who had milder symptoms, showed high mutant loads in endoderm and mesoderm-derived tissues but significantly lower loads in ectoderm-derived hair bulbs. This variability in tissue mutant load complicates genetic counseling and prenatal diagnosis. The findings suggested that hair bulb mtDNA analysis could help understand genotype-phenotype correlations in asymptomatic or mildly symptomatic individuals with high blood mutant loads.