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PRSS12 was first described as one of four genes implicated in nonsyndromic autosomal recessive intellectual disability based on genome-wide linkage and haplotype analyses in consanguineous families (PMID:18452889). No specific PRSS12 variants have been reported in additional unrelated probands, and detailed segregation beyond the initial discovery cohort is lacking, limiting the genetic evidence for pathogenicity.
There are no published functional studies evaluating human PRSS12 variants in neuronal or other relevant cellular models. Yeast decapping assays involving homologous MRT1 alleles do not directly inform PRSS12’s role in human cognition. Consequently, the mechanistic basis of PRSS12 deficiency in intellectual disability remains uncharacterized.
Key Take-home: At present, PRSS12 holds limited clinical utility for diagnostic testing in nonsyndromic autosomal recessive intellectual disability pending replication of pathogenic variants and mechanistic validation.
Gene–Disease AssociationLimitedInitial identification in one linkage study without replication or variant-level evidence Genetic EvidenceLimitedNo pathogenic PRSS12 variants described in unrelated probands or segregation beyond original report Functional EvidenceLimitedNo direct experimental evidence for PRSS12 in neuronal models |