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A rare autosomal recessive mitochondrial disorder characterized by severe epileptic encephalopathy with complex I deficiency and mitochondrial DNA depletion has been linked to biallelic SLC25A10 mutations. In a single reported proband, whole exome sequencing identified a homozygous LoF variant c.304A>T (p.Lys102Ter) (PMID:29211846) segregating with disease in a familial trio. Patient fibroblast studies revealed markedly reduced SLC25A10 transcript levels, aberrant splicing, absence of SLC25A10 protein, impaired glutathione transport, and depletion of key antioxidants NADPH and glutathione (PMID:29211846). A yeast ortholog knockout recapitulated mitochondrial respiration defects, mtDNA depletion, and sensitivity to oxidative stress (PMID:29211846), supporting a loss-of-function mechanism. However, the association remains limited by the single-family report and lack of additional segregation or case series data.
Key take-home: Recessive loss-of-function variants in SLC25A10 disrupt mitochondrial carrier function and precipitate epileptic encephalopathy, warranting further genetic validation in diverse cohorts.
Gene–Disease AssociationLimitedSingle proband with biallelic LoF variants and functional concordance, no additional families or segregation Genetic EvidenceLimitedOne proband with recessive LoF variant c.304A>T (p.Lys102Ter); no additional cases Functional EvidenceModeratePatient fibroblast assays and yeast model demonstrate loss-of-function pathogenic mechanism |