variant analysis in blepharospasm and other neurological disorders.

INTRODUCTION

In preceding work, a deleterious variant [GRCh38/hg38, NC_000008.11:g.22140245G>A, NM_025232.4:c.109C>T, p.Arg37Trp] was found to co-segregate with blepharospasm (BSP) in a large African-American pedigree. Other variants have been reported in genetic screening studies of dystonia. The paralogs, and are associated with spastic paraplegia. The causal contributions of variants to dystonia and other neurological disorders remains indecisive.

METHODS

Sanger sequencing was used to screen subjects ( = 307) with BSP and BSP-plus dystonia affecting additional anatomical segments (BSP+) phenotypes for variants in tools were used to examine the deleteriousness of reported (ClinVar) and previously published variants.

RESULTS

No highly deleterious variant was identified in coding or contiguous splice site regions of in our cohort of 307 subjects. analysis identified numerous deleterious variants in published screening studies of dystonia and several highly deleterious single nucleotide variants in ClinVar.

CONCLUSION

Highly deleterious variants are rare in BSP and BSP+ phenotypes.