Abstract
The kinesin heavy chain isoform 5A (KIF5A) gene, which encodes a microtubule-based motor protein, plays an important role in the transport of organelles in the nerve cells. Mutations in the KIF5A showed a wide phenotypic spectrum from hereditary spastic paraplegia (HSP) to axonal Charcot–Marie–Tooth peripheral neuropathy type 2 (CMT2). This study identified three pathogenic KIF5A mutations in Korean CMT2 patients by whole exome sequencing. Two mutations (p.Arg204Trp and p.Arg280His) were previously reported, but p.Leu558Pro was determined to be a novel de novo mutation. All the mutations were not observed in the healthy controls and were located in highly conserved domains among vertebrate species. The p.Arg204Trp mutation was identified from a CMT2 patient with additional complex phenotypes of HSP, ataxia, fatigability and pyramidal sign, but the p.Arg280His and p.Leu588Pro mutations were identified in each axonal CMT2 patient. The p.Arg204Trp mutation was previously reported in a HSP patient with no CMT symptom. The p.Arg280His mutation was reported in a CMT2 patient, which was similarly with our case. However, it was also once reported in a HSP patient with pes cavus. As the first report in Korea, this study identified three KIF5A mutations as the underlying cause of axonal peripheral neuropathy with or without the HSP phenotype. We confirmed a wide inter- and intra-allelic phenotypic spectrum by the mutations in the KIF5A.
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Acknowledgements
We would like to thank the patients and their families for their participation in this study. This study was supported by the Kongju National University (2014).
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Nam DE, Yoo DH, Choi SS, Choi B-O, and Chung KW declare that they have no conflict of interest.
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Written informed consent was obtained from all the participants or the parents of those younger than 18 years of age according to the protocol approved by the Institutional Review Board of Samsung Medical Center at Sungkyunkwan University (SMC, 2014-08-057-002).
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Nam, D.E., Yoo, D.H., Choi, S.S. et al. Wide phenotypic spectrum in axonal Charcot–Marie–Tooth neuropathy type 2 patients with KIF5A mutations. Genes Genom 40, 77–84 (2018). https://doi.org/10.1007/s13258-017-0612-x
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DOI: https://doi.org/10.1007/s13258-017-0612-x