The most common form of Dopa-responsive dystonia (DRD) is caused by heterozygous mutations in the GTP cyclohydrolase I (GCH1) gene. We screened two unrelated, DRD-symptomatic Chinese Han individuals, for GCH1 gene mutations by direct sequencing. As the clinical manifestations of DRD are highly variable, we also explored the association between genotype and phenotype in all Chinese DRD patients reported so far in the literature, comprising 62 DRD-affected patients from 36 Chinese families. Two novel missense mutations (T94M, L145F) and a novel variant (c. 453 þ 6 G4T) were identified in our two new patients. None of these variants was detected in 200 healthy controls. On the basis of this and other reports, heterozygous mutations were detected in 90.3% of Chinese Han subjects with DRD. Seeming the age of onset for males and females, the mean age was 13 years older in males than in females (P ¼ 0.006). Different mutation types did not show any significant differences in age of onset, gender composition, initial symptoms, or the L-dopa dose that abolished the symptoms. Among DRD patients lacking missense or exon-intron boundary mutations, 68.4% were found to possess a large deletion in GCH1, which were detected by multiplex ligation-dependent probe amplification. Most GCH1 mutations were found to cluster in two regions of the coding sequence, suggesting the probable existence of mutation hotspot for the first time. The genotype-phenotype correlation described here may improve our understanding of DRD in Chinese individuals.
Our findings suggest that the A allele of rs1805874 is associated with risk of Parkinson's disease among the Han Chinese. Our results, combined with previous studies, suggest that rs1805874 is associated with Parkinson's disease in East Asians, but not Caucasians.
Amyotrophic lateral sclerosis (ALS) is a progressive disorder involving the degeneration of motor neurons. ALS shares pathogenic characteristics and genetic risk factors with multiple system atrophy (MSA). Here we examine whether a variant of the COQ2 gene associated with MSA in Japanese is also associated with ALS in Han Chinese. The ligase detection reaction was used to measure the frequency of the V393A variant of COQ2 in 282 patients with ALS and 491 healthy controls. The ALS and control groups showed no significant differences in genotype frequencies (OR 1.298, 95 %CI 0.396-4.253, p = 0.666) or allele frequencies (OR 1.314, 95 %CI 0.403-4.286, p = 0.650) at the V393A locus of COQ2. We also conducted a meta-analysis and combined our data with the previous Japanese research, but still failed to detect an association between V393A and ALS. In conclusion, This case-control study shows no evidence for an association between ALS and the V393A variant of COQ2 in Han Chinese and together with the Japanese research suggests that this polymorphism may not be linked to the risk of ALS in East Asians in general.
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