Early-Onset and Severe Complex Hereditary Spastic Paraplegia Caused by De Novo Variants in SPAST.

ABSTRACT:

Background

Familial hereditary spastic paraplegia (HSP)-SPAST (SPG4) typically presents with a pure HSP phenotype.

Objective

The aim of this study was to delineate the genotypic and phenotypic spectrum of children with de novo HSP-SPAST.

Methods

This study used a systematic cross-sectional analysis of clinical and molecular features.

Results

We report the clinical and molecular spectrum of 40 patients with heterozygous pathogenic de novo variants in SPAST (age range: 2.2-27.7 years). We identified 19 unique variants (16/40 carried the same recurrent variant, p.Arg499His). Symptom onset was in early childhood (median: 11.0 months, interquartile range: 6.0 months) with significant motor and speech delay, followed by progressive ascending spasticity, dystonia, neu

SUBMITTER: Mo A 

PROVIDER: S-EPMC10062395 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature