CAPN11 – benign essential blepharospasm

This evaluation focuses on CAPN11 in the context of benign essential blepharospasm. Recent whole‐exome sequencing analyses of blepharospasm cohorts identified CAPN11 as one of several candidate genes, with deleterious variants observed in at least two independent pedigrees out of a study consisting of 31 subjects from 21 pedigrees (PMID:29770609). Although the gene was not previously linked to isolated blepharospasm, its inclusion in this dataset suggests a potential role that warrants further study.

Segregation analyses in the study were performed in multiple multigenerational families including clear autosomal dominant patterns evident in other genes, and by inference, CAPN11 is considered to follow a similar mode of inheritance. However, specific segregation data such as the number of additional affected relatives carrying CAPN11 variants was not detailed, limiting robust familial evaluation. This lack of granular information on segregating carriers in CAPN11 reduces the overall weight of the genetic evidence.

The genetic evidence for CAPN11 primarily arises from the cohort-based identification of deleterious variants in more than one pedigree. While the study examined various variant classes across several genes, CAPN11 was flagged among genes identified in two or more independent pedigrees. Nonetheless, no explicit variant details (using the required HGVS nomenclature) were provided for CAPN11, which introduces some uncertainty regarding the precise molecular events involved.

From a functional perspective, the available evidence does not include dedicated experimental studies that elucidate the pathogenic mechanism of CAPN11 in blepharospasm. Although functional assessment studies were referenced in the evidence package, no specific cellular or animal models, expression studies, or rescue experiments for CAPN11 were reported. This gap in functional data limits our ability to connect genotype to phenotype through a clear mechanistic pathway.

In summary, the genetic data offers limited evidence for a CAPN11–benign essential blepharospasm association. The identification of deleterious variants in multiple pedigrees from a well‐characterized cohort supports a potential contribution, yet the absence of detailed variant-level and segregation data, paired with a lack of targeted functional assays, confines current confidence to a limited level. Further studies are necessary to validate the gene’s role and clarify the molecular mechanism underlying the phenotype.

Key Take‑home: CAPN11 is a promising candidate gene for benign essential blepharospasm, but additional segregation and functional studies are required to fully support its clinical utility in diagnostic decision‑making.

References

• Molecular genetics & genomic medicine • 2018 • Whole‐exome sequencing for variant discovery in blepharospasm PMID:29770609

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