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Spinocerebellar Ataxia Type 18 (Spinocerebellar Ataxia Type 18) is a rare autosomal dominant neurodegenerative disorder characterized by gait ataxia, pyramidal tract signs, and peripheral neuropathy. A heterozygous missense variant c.514A>G (p.Ile172Val) in IFRD1 was identified by targeted next-generation and confirmed by Sanger sequencing in a Han Chinese pedigree with multiple affected members segregating the variant (PMID:29362493). This variant was previously reported in a five-generation American family but lacks further independent replication and extended segregation data.
Disease-relevant functional studies of IFRD1 in neuronal or cerebellar models are absent. Existing literature describes general IFRD1 expression during development and its role in proprotein convertase activity without modeling the p.Ile172Val change or recapitulating ataxic phenotypes.
Key Take-home: Current evidence for IFRD1 in SCA18 is limited to two kindreds with one recurrent variant; further genetic replication and disease-specific functional assays are required to confirm causality and support clinical testing.
Gene–Disease AssociationLimitedReported in one Han Chinese family with segregation of IFRD1 c.514A>G variant and previously in a single U.S. pedigree; no further independent reports. Genetic EvidenceLimitedSingle missense variant c.514A>G identified in one Han Chinese pedigree with autosomal dominant SCA18; segregation data limited to report ([PMID:29362493]). Functional EvidenceLimitedNo disease-specific functional studies of IFRD1 variants in neuronal or cerebellar models; existing studies describe general IFRD1 expression and enzymatic activity unrelated to ataxia. |