Multiple LRRK2 variants modulate risk of Parkinson disease: a Chinese multicenter study

We and others found two polymorphic LRRK2 (leucine-rich repeat kinase 2) variants (rs34778348:G>A; p.G2385R and rs33949390:G>C; p.R1628P) associated with Parkinson disease (PD) among Chinese patients, but the common worldwide rs34637584:G>A; p.G2019S mutation, was absent. Focusing exclusively on Han Chinese, we first sequenced the coding regions in young onset and familial PD patients and identified 59 variants. We then examined these variants in 250 patients and 250 control subjects. Among the 17 polymorphic variants, five demonstrated different frequency in cases versus controls and were considered in a larger sample of 1,363 patients and 1,251 control subjects. The relative risk of an individual with both p.G2385R and p.R1628P is about 1.9, and this is reduced to 1.5-1.6 if the individual also carries rs7133914:G>C; p.R1398H or rs7308720:C>A: p.N551K. The risk of a carrier with p.R1628P is largely negated if the individual also carries p.R1398H or p.N551K. In dopaminergic neuronal lines, p.R1398H had significantly lower kinase activity, whereas p.G2385R and p.R1628P showed higher kinase activity than wild type. We provided the first evidence that multiple LRRK2 variants exert an individual effect and together modulate the risk of PD among Chinese.

Association of rs1182 polymorphism of the DYT1 gene with primary dystonia in Chinese population

The deletion mutation of glutamate codon (GAG) in the TOR1A gene is a major cause of primary generalized dystonia. Recent genetic studies suggest that the rs1182 polymorphism in the same gene may represent a risk factor for primary dystonia. However, this finding has been inconsistent. Furthermore, no data on such an association in a Chinese population have been published.

Assessment of D216H DYT1 polymorphism in a Chinese primary dystonia patient cohort

The D216H single-nucleotide polymorphism (SNP) (rs1801968) in DYT1 exon 4 has been suggested to be a genetic modifier in primary dystonia.

Diffusion tensor imaging of two unrelated Chinese men with hereditary spastic paraplegia associated with thin corpus callosum

Hereditary spastic paraplegia (HSP) associated with thin corpus callosum is a rare autosomal recessive neurodegenerative disorder characterized by an abnormally thin corpus callosum, normal motor development, slowly progressive spastic paraparesis and cognitive deterioration. To investigate and localize abnormalities in the brains of two Chinese patients with HSP-TCC, with mutations in the spatacsin gene. Diffusion tensor imaging (DTI) was used to determine the mean diffusion (MD) and fractional anisotropy (FA) in the brains of the patients in comparison to 20 healthy subjects. Voxel-based analysis (VBA) of both the diffusion and anisotropy values were performed using statistical parametric mapping (SPM). Significant changes with MD increase and FA reduction were found in the already known lesions including the corpus callosum, cerebellum and thalamus. In addition, changes were also found in regions that appear to be normal in conventional MRI, such as the brain stem, internal capsule, cingulum and subcortical white matter including superior longitudinal fascicle and inferior longitudinal fascicle. Neither increase in FA nor reduction in MD was detected in the brain. Our study provides clear in vivo MR imaging evidence of a more widespread brain involvement of HSP-TCC. MD is more sensitive than FA in detecting lesions in thalamus and subcortical white matter, suggesting that MD may be a better marker of the disease progression.

A novel mutation of the epsilon-sarcoglycan gene in a Chinese family with myoclonus-dystonia syndrome

In a Chinese myoclonus-dystonia syndrome (MDS) family presented with a phenotype including a typical MDS, cervical dystonia, and writer's cramp, genetic analyses revealed a novel 662 + 1insG heterozygous mutation in exon 5 in the epsilon-sarcoglycan (SGCE) gene, leading to a frameshift with a down stream stop codon. Low SGCE mRNA levels were detected in the mutation carriers by real-time PCR, suggesting that the nonsense mutation might interfere with the stability of SGCE mRNA. This is the first report on Chinese with a SGCE mutation leading to MDS. Our data support the fact that same mutation of SGCE gene can lead to a varied phenotype, even in the same family.