A Novel Frameshift Variant in the SPAST Gene Causing Hereditary Spastic Paraplegia in a Bulgarian-Turkish Family.

ABSTRACT:

Background

Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by progressive lower-limb spasticity and weakness. SPAST mutations are the most common cause of autosomal dominant HSP (SPG4). However, many pathogenic SPAST variants are unique and genetic data from underrepresented communities remain limited.

Methods

Whole-exome sequencing (WES) was performed on the index patient with HSP. Variant annotation tools included Ensembl VEP, LOFTEE, CADD, SIFT, PolyPhen-2, MutationTaster, and SpliceAI. Variant interpretation followed ACMG/AMP guidelines. Clinical evaluation and family history supported phenotypic correlation and segregation.

Results

A novel heterozygous frameshift variant in SPAST

SUBMITTER: Levkova M 

PROVIDER: S-EPMC12566801 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature