Genetic analysis of SPG4 and SPG3A genes in a cohort of Chinese patients with hereditary spastic paraplegia

Abstract Hereditary spastic paraplegia (HSP or SPG) is a group of genetically and clinically heterogeneous neurodegenerative disorders. At least 52 different gene loci have been identified so far, involving autosomal dominant (AD), autosomal recessive (AR), X-linked (XL), and maternal inheritance. Mutations in the SPAST (SPG4) and ATL1 (SPG3A) genes are responsible for about 50% of pure AD-HSP patients. In this study, SPAST and ATL1 mutations were screened in 36 unrelated HSP patients (17 probands with AD family history and 19 sporadic HSP patients) by direct sequencing and multiplex ligation dependent probe amplification (MLPA). We identified 3 micro-mutations and 2 exon deletions in SPAST gene and 2 micro-mutations in ATL1 gene. Four of five micro-mutations were novel and del. ex. 13–15 in SPAST was not reported previously. In this cohort of Chinese patients with spastic paraplegia, SPAST and ATL1 mutations were found in 5 of 17 HSP probands with AD family history and in 2 of 19 sporadic HSP patients. Four novel micro-mutations and one novel exon deletion were identified, which broadened the mutational spectrum of the genes.