Two novel mutations in the Spastin gene of Chinese patients with hereditary spastic paraplegia.

BACKGROUND AND PURPOSE: Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous group of neurodegenerative diseases. Mutations in the spastin (SPG4) gene are responsible for approximately 40% of autosomal dominant HSP (AD-HSP) and 6.5-18% of sporadic cases. METHODS: Spastin mutations were screened in 11 AD-HSP families and 11 sporadic cases by direct sequencing and MLPA assay. Novel mutations were detected in 100 healthy controls by PCR-RFLP. RESULTS: We identified seven different spastin mutations in five probands and one sporadic patient. Two of seven mutations were novel. The c.458delT was a pathogenic mutation, but the effect of c.1724 G>T remained unknown. CONCLUSIONS: This study allowed us to estimate the frequency of the SPG4 mutations in Chinese at 45% (5/11) in families with AD-HSP and 9% (1/11) in sporadic cases. In addition, our data showed p.T614I was not associated with congenital arachnoid cysts.

Analysis of Lingo1 variant in sporadic and familial essential tremor among Asians.

OBJECTIVE - Genome-wide association study (GWAS) has identified a variant in LINGO1 (rs9652490) that increases the risk of essential tremor (ET) among Caucasians. It has been suggested that among Asians, the risk variant is relevant only for the familial forms of ET. We investigated the association of the rs9652490 variant with sporadic and familial ET in a Chinese population and conducted a pooled analysis to compare the potential differential effect between sporadic and familial ET. METHODS - rs9652490 was genotyped by direct sequencing in 117 ET and 160 controls in a Chinese population. Previous published data from another Asian population were included in the meta-analysis. RESULT - There were no significant differences in the minor allele frequency and genotype frequency between ET and controls in our Chinese population. However, in the pooled analysis involving 1201 subjects, patients with ET had a higher proportion of GG genotype compared to controls. Logistic regression analysis revealed that G allele increased the risk of ET via a recessive model. In both familial ET and sporadic ET, the G allele increased the risk via a recessive model. CONCLUSION - While we could not demonstrate a significant association of the rs9652490 variant in our own study, pooled analysis of a much larger cohort revealed for the first time that the variant increased the risk in both familial and sporadic forms of ET among Asians, though the effect was stronger in familial ET.