Evaluation of loss of function as an explanation for SPG4-based hereditary spastic paraplegia.

ABSTRACT: The spectrum of mutations (missense, non-sense and splice-site) associated with hereditary spastic paraplegia 4 (HSP-SPG4) (SPG4:OMIM#182601) has suggested that this autosomal dominant disease results from loss of function. Because the protein encoded by SPG4, termed spastin, is a microtubule-severing enzyme, a loss-of-function scenario for the disease suggests that corticospinal axons degenerate due to inadequate microtubule severing resulting from inactivation of one spastin allele. Lending more complexity to the situation, there are two major isoforms of spastin (M1 and M87) translated from two start codons. M87 is widely expressed, while M1 is appreciably detected only in adult spinal cord. Here, we focused on four HSP-associated mutations of the SPG4 gene located outside of the AAA re

SUBMITTER: Solowska JM 

PROVIDER: S-EPMC2893808 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature