Mutation scanning of the COQ2 gene in ethnic Chinese patients with multiple-system atrophy

Multiple-system atrophy (MSA) is a fatal neurodegenerative disorder with unknown etiology. It is widely considered to be a nongenetic disorder, but accumulating evidence suggests that several genes are linked to MSA. Recently, functionally impaired variants in the coenzyme Q2 4-hydroxybenzoate polyprenyltransferase (COQ2) gene have been reported to increase the risk of MSA in familial and sporadic Japanese patients. In this study, we investigated the mutation spectrum of COQ2 and analyzed the association between the common variant Val393Ala in exon 7 of COQ2 and MSA in a Chinese population. This study included 312 sporadic MSA patients from the Department of Neurology, West China Hospital of Sichuan University. All 7 exons of COQ2 in all the patients and exon 7 in 598 healthy controls (HCs) were directly sequenced. Novel candidate mutations and variations were confirmed by direct sequencing in 300 HCs. Two novel nonsynonymous variants, including p.R173H and p.N386I, and a reported missense variant, p.L162F, were found in 4 patients (p.R173H in 2 patients). However, the Val393Ala variant was not detected in the above 4 patients. Thirteen MSA patients (4.17%) and 18 controls (3.01%) had the heterozygous variant (Val393Ala/NM) of COQ2. No significant differences existed in the genotype frequency and minor allele frequency of Val393Ala between patients and controls or between MSA characterized predominantly by cerebellar ataxia and by pakinsonism groups. The mutation frequency of COQ2 is 1.28% in a Chinese MSA population. The common variant Val393Ala in COQ2 does not appear to be associated with MSA in ethnic Chinese.