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Biallelic loss-of-function variants in MRPS36 have been identified in autosomal recessive Leigh syndrome (Leigh syndrome). Two affected siblings from a single consanguineous family presented with global developmental delay, movement abnormalities, hepatic failure, and early-onset lactic acidosis. Exome sequencing revealed a homozygous nonsense variant c.283G>T (p.Glu95Ter) in MRPS36, which segregated with disease in both sibs (PMID:38685873).
Patient fibroblasts exhibited a marked reduction in 2-oxoglutarate dehydrogenase complex (OGDHC) enzymatic activity and structural modeling demonstrated destabilization of the OGDHC complex due to loss of nine critical residues (PMID:38685873). These functional data concord with the clinical phenotype and support a loss-of-function mechanism.
Gene–Disease AssociationLimitedTwo probands from one family with homozygous MRPS36 nonsense variant; supportive functional data (PMID:38685873). Genetic EvidenceLimitedHomozygous c.283G>T (p.Glu95Ter) segregates with disease in two affected siblings in a single pedigree (PMID:38685873). Functional EvidenceModeratePatient fibroblasts show significantly reduced OGDHC enzymatic activity and structural destabilization consistent with loss-of-function (PMID:38685873). |