A novel truncating variant of SPAST associated with hereditary spastic paraplegia indicates a haploinsufficiency pathogenic mechanism.

ABSTRACT:

Introduction

Hereditary spastic paraplegias (HSPs) are genetic neurodegenerative diseases. The most common form of pure HSP that is inherited in an autosomal dominant manner is spastic paraplegia type 4 (SPG4), which is caused by mutations in the SPAST gene. Different theories have been proposed as the mechanism underlying SPAST-HSP for different types of genetic mutations, including gain- and loss-of-function mechanisms. To better understand the mutation mechanisms, we performed genetic analysis and investigated a truncating SPAST variant that segregated with disease in one family.

Objectives and methods

We described a pure HSP pedigree with family members across four generations. We performed genetic analysis and investigated a novel frameshift pathoge

SUBMITTER: Nan H 

PROVIDER: S-EPMC9703935 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature