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Sequencing of the SAG coding and flanking intronic regions in 272 unrelated patients with autosomal dominant (n = 177) or autosomal recessive (n = 85) retinitis pigmentosa and stationary night blindness revealed six heterozygous missense variants—Arg84Cys, Thr125Met, Val378Ile, Pro364Leu, Arg384Cys—none of which co-segregated with disease or were present in a biallelic state, leading to the conclusion that SAG is not a cause of retinitis pigmentosa outside of Oguchi disease (PMID:9501883).
No subsequent case reports or series have documented pathogenic SAG variants in retinitis pigmentosa, and no functional studies have demonstrated variant-specific effects in the context of photoreceptor degeneration. Established assays of arrestin binding and conformational dynamics do not address RP-relevant pathogenicity.
Key Take-home: Current evidence refutes a causal role for SAG variants in retinitis pigmentosa; routine SAG testing is not indicated for RP diagnostic work-up.
Gene–Disease AssociationRefutedSequencing in 272 unrelated RP patients ([PMID:9501883]) identified six heterozygous missense variants that did not co-segregate or occur in biallelic state, refuting the association. Genetic EvidenceDisputedSix heterozygous missense variants in unrelated probands lacked segregation or biallelic presentation ([PMID:9501883]). Functional EvidenceLimitedNo functional data support SAG variant pathogenicity in RP; existing assays examine arrestin biochemistry unrelated to photoreceptor degeneration. |