REEP4 variant analysis in blepharospasm and other neurological disorders
Samira Saeirad1, Mark S LeDoux1,2
1Department of Psychology, University of Memphis, Memphis, TN, United States.
Dystonia (Lausanne, Switzerland)
|September 12, 2024
Summary
Highly deleterious REEP4 gene variants are uncommon in blepharospasm and dystonia phenotypes. Further research is needed to clarify the role of REEP4 in neurological disorders.
Area of Science:
- Genetics
- Neurology
- Molecular Biology
Background:
- A specific REEP4 variant was previously linked to blepharospasm (BSP) in a large African-American family.
- Other REEP4 variants have been implicated in dystonia, and its paralogs (REEP1, REEP2) are associated with spastic paraplegia.
- The exact role of REEP4 variants in causing dystonia and other neurological conditions remains unclear.
Purpose of the Study:
- To investigate the frequency of deleterious REEP4 variants in individuals with blepharospasm (BSP) and BSP-plus (BSP+) dystonia.
- To assess the pathogenicity of known and identified REEP4 variants using in silico tools.
Main Methods:
- Sanger sequencing was performed on 307 subjects with BSP and BSP+ phenotypes to screen for REEP4 variants.
- In silico analysis was employed to evaluate the deleteriousness of reported and previously identified REEP4 variants.
Main Results:
- No highly deleterious REEP4 variants were found in the coding or splice site regions of the 307 subjects studied.
- In silico analysis revealed numerous deleterious REEP4 variants in published dystonia studies and several highly deleterious variants in ClinVar.
Conclusions:
- Highly deleterious REEP4 variants appear to be rare in patients presenting with blepharospasm and related dystonia phenotypes.
- The findings suggest that REEP4 may not be a common cause of these specific neurological conditions, warranting further investigation into other genetic factors.
