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The association between HS1BP3 and benign essential blepharospasm is currently supported by limited genetic evidence. In a whole‐exome sequencing study of 31 subjects from 21 independent pedigrees with blepharospasm (PMID:29770609), a deleterious missense variant, c.94C>A (p.Gly32Cys), was identified in HS1BP3. This variant was observed to segregate in a father‐son pair, suggesting an autosomal dominant mode of inheritance, although segregation was limited to only one additional affected relative (PMID:29770609).
The genetic evidence for HS1BP3 is restricted to this single deleterious variant without additional independent replication. Although the overall study reviewed several candidate genes, the data for HS1BP3 remains minimal when compared to more extensively validated associations. As such, the genetic support is classified as limited due to the presence of only one reported variant and minimal segregation evidence.
On the experimental front, functional assessments of HS1BP3 have been carried out in studies focused on other movement disorders such as Parkinson disease, essential tremor, and Bell palsy (PMID:17353387; PMID:19524641). These studies did not demonstrate functional effects of the HS1BP3 variant in a manner that is concordant with the blepharospasm phenotype. Hence, the functional evidence linking HS1BP3 to benign essential blepharospasm is also considered limited.
In summary, while a deleterious variant in HS1BP3 was identified in a family with blepharospasm suggesting an autosomal dominant inheritance pattern, the overall evidence remains preliminary with limited genetic and functional support. Additional studies with larger cohorts and targeted functional assays are required to definitively establish the gene‐disease relationship.
Key Take‑home: While the HS1BP3 variant c.94C>A (p.Gly32Cys) shows some promise for diagnostic consideration in benign essential blepharospasm, its current evidence is insufficient for broad clinical utility.
Gene–Disease AssociationLimitedThe association is based on the identification of a single deleterious missense variant in a father‐son pair (PMID:29770609). The limited segregation and lack of additional supporting data result in a classification of limited evidence. Genetic EvidenceLimitedOnly one HS1BP3 variant, c.94C>A (p.Gly32Cys), was reported with minimal segregation data, providing limited genetic support for its role in benign essential blepharospasm. Functional EvidenceLimitedFunctional studies conducted in the context of other neurological disorders did not replicate findings specific to benign essential blepharospasm, thereby offering limited experimental support. |