Variant Synonymizer: Platform to identify mutations defined in different ways is available now!
Over 2,000 gene–disease validation summaries are now available—no login required!
In a detailed case report (PMID:18696223), a 13-year-old male with autism, severe developmental delay, facial dysmorphism, and self‑mutilation was found to carry a de novo duplication of a 6.14–6.58 Mb region on chromosome 8p21. This region harbors 36 genes, with STMN4 being highlighted as a strong candidate based on its robust transcription in brain tissues. The patient’s phenotype is consistent with disruptions in neuronal development and aligns with the neurodevelopmental spectrum observed in autism. This singular observation offers preliminary genetic evidence implicating STMN4 in autism spectrum disorder, yet the limited number of independent probands curtails broader clinical confidence. The absence of additional familial segregation data further restricts the strength of this association. Overall, this case report contributes to the growing, but still limited, evidence for a role of STMN4 in the pathogenesis of autism.
A subsequent multi‐patient study (PMID:26931105) explored common variants in the chromosome 8p21.2–8p21.1 region. Although the genome‑wide association approach initially identified SNPs near STMN4 that approached significance for association with restricted and repetitive behaviors—a core feature in autism—the findings did not achieve robust replication in an independent cohort. This inconsistency, combined with the absence of additional functional assessment data, further limits the clinical validity of STMN4 as a definitive contributor to the etiology of autism. While these multi‑patient and case‑based evidences suggest a potential involvement of STMN4, the conflicting replication outcomes and lack of corroborative experimental data confine the overall gene‑disease association to a limited level. Key take‑home: Current evidence warrants cautious interpretation of STMN4’s role in autism, and more extensive genetic and functional studies are needed to refine its clinical utility.
Gene–Disease AssociationLimitedA single de novo duplication case (PMID:18696223) supports an association with autism, but non‐replicating GWAS signals (PMID:26931105) and limited segregation data restrict the overall evidence. Genetic EvidenceLimitedThe genetic evidence is primarily drawn from one de novo duplication study and nominal GWAS associations that did not replicate, providing only preliminary support for STMN4’s involvement in autism. Functional EvidenceLimitedNo functional assessment studies have been reported to elucidate the mechanistic role of STMN4 in autism, limiting insights into its pathogenicity. |