SPON1 – Schizophrenia

The association between SPON1 (HGNC:11252) and schizophrenia (MONDO_0005090) is supported by preliminary genetic evidence from whole‑exome sequencing studies. In a study of two families, each with two affected siblings (PMID:30226068), frameshifting indels in SPON1 were identified, including a representative variant, c.456del (p.Lys153SerfsTer4). This variant meets the ClinGen guidelines for rigorous HGVS nomenclature, and bioinformatic analyses predict a damaging loss‑of‑function effect. Segregation analysis within these families showed that the variant co‑segregated with the schizophrenia phenotype, although the total number of unrelated probands remains modest. The genetic evidence is based solely on these familial case reports and has not yet been independently replicated, limiting the overall strength of the association.

No direct functional studies have been performed in neural models to elucidate the mechanism by which SPON1 variants may predispose to schizophrenia. Although a loss‑of‑function effect is inferred from the frameshift nature of the reported variant, there is an absence of specific experimental validation in relevant cell or animal models. Together, the genetic findings provide a promising but preliminary link between SPON1 and schizophrenia that may inform future studies. Key take‑home: While SPON1 presents as a candidate gene for schizophrenia, further genetic and functional investigations are required to confirm its clinical utility in diagnosis and potential therapeutic targeting.

References

• Bratislavske lekarske listy • 2018 • Determination of candidate genes involved in schizophrenia using the whole‑exome sequencing PMID:30226068

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