Mutation screening of PLA2G6 in Japanese patients with early onset dystonia-parkinsonism
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A recessive mutation in PLA2G6, which is known to cause infantile neuroaxonal dystrophy (INAD) and neurodegeneration associated with brain iron accumulation (NBIA), has recently been shown to be responsible for PARK14-linked dystonia-parkinsonism. To study the frequency of PLA2G6 mutations, including those caused by gene rearrangement in patients with parkinsonism, we performed direct sequencing and investigated copy number variations (CNVs) of this gene in 109 Japanese patients with parkinsonism. Direct sequencing revealed a homozygous mutation (c.1495G>A; p.A499T), which is likely to be pathogenic and is already registered as rs141045127, and two compound-heterozygous mutations we have previously reported. No CNVs in PLA2G6 were detected in our subjects. Our results suggest that CNV in PLA2G6 is rare in parkinsonism, at least in the Japanese population, in contrast to the reports of its frequency in INAD. Further large studies in various populations are warranted to elucidate what causes the difference in frequencies of PLA2G6 rearrangement mutations between INAD and dystonia-parkinsonism.
KeywordsPLA2G6 PARK14 Parkinsonism Copy number variation (CNV)
The authors thank all the participants in this study.
Compliance with ethical standards
Conflict of interest
This work was supported by Grants-in-Aid for Scientific Research (KAKENHI) (to MF, 25461291 and 16K09676, to YL, 25860725 and 16K09700, to HT, 25461292, and to NH, 24390224 and 15H04842) from the Japan Society for the Promotion of Science (JSPS), Grants-in-Aid for Scientific Research on Innovative Areas (to MF 25129707, and to NH, 23111003), a Grant-in-Aid for the Program for the Strategic Research Foundation at Private Universities from the Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT); and a Health Labour Sciences Research Grant (H26-Nanchitou-Nan-Ippan-085 to NH; H26-Itaku-Nan-Ippan-037 to NH) from the Japanese Ministry of Health, Labour and Welfare (MHLW).
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