Background Recent genetic progress has allowed for the molecular diagnosis of Parkinson's disease. However, genetic causes of PD vary widely in different ethnicities. Mutational frequencies and clinical phenotypes of genes associated with PD in Asian populations are largely unknown. The objective of this study was to identify the mutational frequencies and clinical spectrums of multiple PD‐causative genes in a Taiwanese PD cohort. Methods A total of 571 participants including 324 patients with early‐onset parkinsonism (onset age, <50 years) and 247 parkinsonism pedigrees were recruited at a tertiary referral center in Taiwan from 2002 to 2017. Genetic causes were identified by an integrated approach including gene dosage analysis, a targeted next‐generation sequencing panel containing 40 known PD‐causative genes, repeat‐primed polymerase chain reaction, and whole‐exome sequencing analysis. Results Thirty of the 324 patients with early‐onset parkinsonism (9.3%) were found to carry mutations in Parkin , PINK1 , or PLA2G6 or had increased trinucleotide repeats in SCA8 . Twenty‐nine of 109 probands with autosomal‐recessive inheritance of parkinsonism (26.6%) were found to carry mutations in Parkin , PINK1 , GBA , or HTRA2 . The genetic causes for the 138 probands with an autosomal‐dominant inheritance pattern of parkinsonism were more heterogeneous. Seventeen probands (12.3%) carried pathogenic mutations in LRRK2 , VPS35 , MAPT , GBA , DNAJC13 , C9orf72 , SCA3, or SCA17 . A novel missense mutation in the UQCRC1 gene was found in a family with autosomal‐dominant inheritance parkinsonism via whole‐exome sequencing analysis. Conclusions Our findings provide a better understanding of the genetic architecture of PD in eastern Asia and broaden the clinical spectrum of PD‐causing mutations. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

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Mutations in transmembrane protein 230 (TMEM230) have recently been reported to be associated with Parkinson's disease (PD) in a North American population. A highly prevalent mutation, c.550_552delTAGinsCCCGGG (p.*184ProGlyext*5) was found in 3.1% of Chinese familial PD patients. However, subsequent studies failed to replicate these findings in different populations. Our objective was to confirm the role of this gene in a large number of PD patients and controls in a Taiwanese population. Among 1,672 participants, we sequenced all coding exons and exon-intron boundary junctions of the TMEM230 gene in 180 probands with familial PD. We also genotyped the potential pathogenic variants identified and the previously reported mutations (p.Arg141Leu, p.Tyr92Cys, p.*184Trpext*5, and p.*184ProGlyext*5) in an additional cohort of 500 patients with sporadic PD, and 992 age and gender-matched neurologically normal control subjects. We did not find any of the previously reported mutations, but we observed one novel missense exonic variant, c.G68A (p.Arg23Gln), in one patient with familial PD, and two patients with sporadic PD in a heterozygous state. However, subsequent analysis of this variant in 992 controls did not find any significant associations between p.Arg23Gln and the risk of PD (0.44% vs. 0.30%, p = 0.22). Our findings suggest that genetic variants of TMEM230 do not play a major role in PD in our Taiwanese population. Further experimental studies are warranted to confirm the pathogenicity of this gene in PD disease process.