{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T16:11:18Z","timestamp":1781194278766,"version":"3.54.1"},"reference-count":35,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,4,2]],"date-time":"2019-04-02T00:00:00Z","timestamp":1554163200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005795","name":"Chang Gung Memorial Hospital, Linkou","doi-asserted-by":"publisher","award":["CMRPG3G3H0312"],"award-info":[{"award-number":["CMRPG3G3H0312"]}],"id":[{"id":"10.13039\/501100005795","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005795","name":"Chang Gung Memorial Hospital, Linkou","doi-asserted-by":"publisher","award":["CMRPG3H0311"],"award-info":[{"award-number":["CMRPG3H0311"]}],"id":[{"id":"10.13039\/501100005795","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Polymerase gamma (<jats:italic>POLG<\/jats:italic>) is an enzyme responsible for the replication and repair of mitochondrial DNA. Mutations in <jats:italic>POLG<\/jats:italic> may cause variable clinical manifestations, including parkinsonism, epilepsy, cerebellar ataxia, neuropathy, and progressive external ophthalmoplegia. However, mutations of this gene are rare in patients with typical Parkinson's disease (PD). We report a man (current age: 59\u00a0years) without any underlying disease presenting with right\u2010hand tremor at the age of 39\u00a0years, followed by slow movement, rigidity, and postural instability. He developed motor fluctuation and levodopa\u2010induced dyskinesia 8\u00a0years later. At the age of 58\u00a0years, cognitive decline and visual hallucination ensued; he was institutionalized thereafter. We used multiplex ligation\u2010dependent probe amplification, which demonstrated no large deletions or duplications of relevant PD genes. Next, targeted sequencing panel covering 51 genes causative for PD was applied for the proband; it revealed a heterozygous missense substitution R964C in <jats:italic>POLG<\/jats:italic> and a heterozygous missense substitution L444P in <jats:italic>GBA<\/jats:italic>. The patient's father, who had been diagnosed as having PD and type 2 diabetes mellitus at the age of 70\u00a0years, demonstrated identical mutations. This is the first report of familial PD combined with <jats:italic>POLG<\/jats:italic> R964C and <jats:italic>GBA<\/jats:italic> L444P mutations. Two pathogenic gene mutations potentially cause double hit in pathological neurodegeneration. This finding extends our understanding of the PD genotype\u2013phenotype correlation.<\/jats:p>","DOI":"10.1002\/brb3.1281","type":"journal-article","created":{"date-parts":[[2019,4,3]],"date-time":"2019-04-03T04:45:14Z","timestamp":1554266714000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["<i>POLG<\/i> R964C and <i>GBA<\/i> L444P mutations in familial Parkinson's disease: Case report and literature review"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5258-5950","authenticated-orcid":false,"given":"Pei\u2010Chen","family":"Hsieh","sequence":"first","affiliation":[{"name":"Department of Neurology Chang Gung Memorial Hospital at Linkou Medical Center Taoyuan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun\u2010Chieh","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology Chang Gung Memorial Hospital at Linkou 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