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In a consanguineous family with autosomal recessive cerebellar ataxia, oculomotor apraxia, and sensorimotor neuropathy, homozygous c.1885C>T (p.Pro629Ser) in PIK3R5 was identified by positional mapping to chr17p12–p13 and sequencing, and was absent in 477 normal controls (PMID:22065524). Segregation of this variant in two affected siblings supports a role in disease pathogenesis (2 affected relatives) (PMID:22065524).
In a follow‐up genetic screen of 52 Brazilian patients with AOA phenotype, no pathogenic PIK3R5 variants were detected (PMID:35426160). Although preliminary protein characterization implies PIK3R5 involvement in cerebellar development, no functional assays or replication cohorts have been reported. Overall, the association remains limited pending additional unrelated cases and experimental validation.
Key Take‐home: PIK3R5 should be considered in diagnostic panels for autosomal recessive ataxia with oculomotor apraxia when common genes are negative, but further evidence is required for definitive clinical utility.
Gene–Disease AssociationLimitedSingle consanguineous family with homozygous missense in PIK3R5 segregating with disease; absence of additional cases and negative subsequent cohort screen Genetic EvidenceLimitedOne homozygous variant in one family (2 probands) segregated; no additional probands identified in 52 patients and variant absent in 477 controls Functional EvidenceNo evidenceNo functional assays or rescue experiments have been reported |