<b>Results:</b> Fifty four patients with genetically confirmed HSP diagnosis, 36 with spastic paraplegia type 4 (SPG4), 5 SPG11, 4 SPG5, 4 cerebrotendinous xanthomatosis (CTX), 3 SPG7 and 2 SPG3A, and 10 healthy, unrelated control subjects, with similar age, sex, and education participated in the study.
Three genetic types, SPG3 (ATL1), SPG4 (SPAST) and SPG31 (REEP1), appear predominantly and may account for up to 50% of autosomal dominant hereditary spastic paraplegias (AD-HSPs).
Furthermore, we propose that genomic deletions encompassing the final exon of SPAST may affect expression of SLC30A6, the most proximal downstream locus and a gene that has been implicated in the pathogenesis of Alzheimer disease, potentially explaining recent reports of dementia in selected SPG4 patients.
These data suggest that varying spastin RNA levels are found in out-of-frame and missense spastin mutations and imply different mechanisms involved in the molecular pathology of SPG4 linked HSP.
We aim to extend the mutation spectrum of spastic paraplegia 4 (SPG4) and carried out experiment in vitro to explore the influence of the SPAST gene mutation on the function of corresponding protein.
Human skin fibroblasts were isolated from a 40-year-old hereditary spastic paraplegia patient carrying an intronic splice site mutation (c.1687+2T>A) in SPAST, leading to hereditary spastic paraplegia type 4 (SPG4).
Three genetic types, SPG3 (ATL1), SPG4 (SPAST) and SPG31 (REEP1), appear predominantly and may account for up to 50% of autosomal dominant hereditary spastic paraplegias (AD-HSPs).
Molecular spectrum of the SPAST, ATL1 and REEP1 gene mutations associated with the most common hereditary spastic paraplegias in a group of Polish patients.