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In a whole‑exome sequencing study of two families (PMID:30226068), frameshifting indels in SEMA3B were identified in four probands. In the first family, two siblings presented with schizophrenia while both parents were unaffected, and a similar pattern was seen in the second family. The observed indels, including one representative variant (c.450_451del (p.Lys150SerfsTer5)), are predicted to result in loss‑of‑function. These findings provide limited genetic evidence for an association with schizophrenia, although the number of probands is small and warrants further replication.
Despite the observed segregation, functional studies directly linking SEMA3B to schizophrenia are currently lacking. Notably, functional assessments of SEMA3B have been performed in the context of gastric cardia adenocarcinoma (PMID:30656427), which does not recapitulate the neuropsychiatric phenotype. Integration of the genetic data suggests SEMA3B as a candidate gene for schizophrenia with preliminary clinical utility, but additional studies are necessary to substantiate its role in disease pathogenesis.
Gene–Disease AssociationLimitedFour probands from 2 independent families (PMID:30226068) exhibit segregating frameshift indels in SEMA3B, providing preliminary evidence that is limited by the modest sample size. Genetic EvidenceLimitedThe detection of a frameshifting indel (c.450_451del (p.Lys150SerfsTer5)) in SEMA3B in 4 affected individuals across 2 families supports a potential role in schizophrenia, though the overall genetic data remain sparse. Functional EvidenceLimitedCurrent functional studies have examined SEMA3B in the context of gastric cardia adenocarcinoma (PMID:30656427), limiting mechanistic insights into its role in schizophrenia. |