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PDSS2 encodes decaprenyl diphosphate synthase subunit 2, catalyzing the first step in CoQ10 biosynthesis. A single infant with severe Leigh syndrome, nephrotic syndrome (HP:0000100), and CoQ10 deficiency in muscle and fibroblasts was reported to harbor compound heterozygous PDSS2 variants c.964C>T (p.Gln322Ter) and c.1145C>T (p.Ser382Leu) in trans (PMID:17186472). Parental segregation confirmed each variant was inherited from an unaffected carrier. Functional assays using radiolabeled substrates in patient fibroblasts demonstrated a severe defect in decaprenyl diphosphate synthase activity (PMID:17186472). This report establishes a loss-of-function mechanism underlying primary CoQ10 deficiency manifesting as autosomal recessive Leigh syndrome with renal involvement. As only a single family has been described, the genetic evidence is currently limited, though functional data provide moderate support for pathogenicity. Key take-home: PDSS2 gene analysis should be considered in patients with Leigh syndrome and nephropathy to enable early CoQ10 supplementation.
Gene–Disease AssociationLimitedSingle reported proband with compound heterozygous PDSS2 variants and supportive functional data Genetic EvidenceLimitedOne proband with compound heterozygous LoF and missense variants in trans; parental segregation ([PMID:17186472]) Functional EvidenceModeratePatient fibroblast assays show severe decaprenyl diphosphate synthase deficiency ([PMID:17186472]) |