Fan T.-S.CHIN-HSIEN LINLin H.-I.Chen M.-L.RUEY-MEEI WU2020-02-252020-02-2520171552-4841https://scholars.lib.ntu.edu.tw/handle/123456789/463618Mutations 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. ? 2017 Wiley Periodicals, Inc.[SDGs]SDG3amino acid substitution; Article; autosomal dominant inheritance; comparative study; computer model; controlled study; exon; familial Parkinson disease; gene; genetic association; genetic screening; genetic variation; genotype; genotype phenotype correlation; heterozygosity; human; intron; major clinical study; missense mutation; mutational analysis; Parkinson disease; pathogenicity; priority journal; sequence analysis; sequence homology; sporadic Parkinson disease; Taiwanese; TMEM230 gene; adult; aged; case control study; cohort analysis; exon; female; follow up; genetic association study; genetics; male; middle aged; mutation; Parkinson disease; prognosis; Taiwan; membrane protein; TMEM230 protein, human; Adult; Aged; Case-Control Studies; Cohort Studies; Exons; Female; Follow-Up Studies; Genetic Association Studies; Genotype; Humans; Male; Membrane Proteins; Middle Aged; Mutation; Parkinson Disease; Prognosis; Taiwanjournal article10.1002/ajmg.b.32576287669102-s2.0-85026644867