Dysfunctional Homozygous VRK1-D263G Variant Impairs the Assembly of Cajal Bodies and DNA Damage Response in Hereditary Spastic Paraplegia.

ABSTRACT:

Background and objectives

To conduct a genetic and molecular functional study of a family with members affected of hereditary spastic paraplegia (HSP) of unknown origin and carrying a novel pathogenic vaccinia-related kinase 1 (VRK1) variant.

Methods

Whole-exome sequencing was performed in 2 patients, and their parents diagnosed with HSP. The novel VRK1 variant was detected by whole-exome sequencing, molecularly modeled and biochemically characterized in kinase assays. Functionally, we studied the role of this VRK1 variant in DNA damage response and its effect on the assembly of Cajal bodies (CBs).

Results

We have identified a very rare homozygous variant VRK1-D263G with a neurologic phenotype associated with HSP and moderate intellectual disabili

SUBMITTER: Morejon-Garcia P 

PROVIDER: S-EPMC8422991 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature