Abstract
PLA2G6-associated neurodegeneration (PLAN) comprises heterogeneous neurodegenerative disorders, including infantile neuroaxonal dystrophy, neurodegeneration with brain iron accumulation 2B, and Parkinson disease 14 (PARK14). In addition, very recently, PLA2G6 mutations have been reported to represent a phenotype of hereditary spastic paraplegia (HSP). In this study, we screened 383 HSP families to clarify the frequency of PLA2G6 mutations in the Japan Spastic Paraplegia Research Consortium, and revealed the clinical characteristics of HSP with PLA2G6 mutations. We found three families with compound heterozygous mutations of the PLA2G6 gene, c.517 C > T/c.1634A > G, c.662 T > C/c.991 G > T, and c.1187-2 A > G/c.1933C > T, and one family with a homozygous mutation of the PLA2G6 gene, c.1904G > A/c.1904G > A. All three families with compound heterozygous mutations presented a uniform phenotype of a complicated form of HSP with infantile/child-onset spastic paraplegia, cerebellar ataxia, and mental retardation. On the other hand, the family with a homozygous mutation presented a late-onset complicated form of HSP with parkinsonism. This study may extend the clinical and genetic findings for PLAN.
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09 November 2018
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Acknowledgements
We thank all the participants and cooperating doctors in the JASPAC. This work was supported by Grants-in-Aid from the Research Committee for Ataxic Disease (YT), the Ministry of Health, Labor and Welfare, Japan, JSPS KAKENHI Grant Numbers JP17K17772 (KK) and JP18K07495 (YT) from the Ministry of Education, Culture, Sports, Science, and Technology, Japan, and grants for AMED under Grant Numbers JP 17ek0109078 (YT) and 18kk0205001h0003 (ST).
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Koh, K., Ichinose, Y., Ishiura, H. et al. PLA2G6-associated neurodegeneration presenting as a complicated form of hereditary spastic paraplegia. J Hum Genet 64, 55–59 (2019). https://doi.org/10.1038/s10038-018-0519-7
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DOI: https://doi.org/10.1038/s10038-018-0519-7
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