Extended phenotypic spectrum of KIF5A mutations: From spastic paraplegia to axonal neuropathy.

Yo Tsen Liu, Matilde Laurá, Joshua Hersheson, Alejandro Horga, Zane Jaunmuktane, Sebastian Brandner, Alan Pittman, Deborah Hughes, James M. Polke, Mary G. Sweeney, Christos Proukakis, John C. Janssen, Michaela Auer-Grumbach, Stephan L Zuchner, Kevin G. Shields, Mary M. Reilly, Henry Houlden

Research output: Contribution to journalArticle

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Abstract

To establish the phenotypic spectrum of KIF5A mutations and to investigate whether KIF5A mutations cause axonal neuropathy associated with hereditary spastic paraplegia (HSP) or typical Charcot-Marie-Tooth disease type 2 (CMT2). KIF5A sequencing of the motor-domain coding exons was performed in 186 patients with the clinical diagnosis of HSP and in 215 patients with typical CMT2. Another 66 patients with HSP or CMT2 with pyramidal signs were sequenced for all exons of KIF5A by targeted resequencing. One additional patient was genetically diagnosed by whole-exome sequencing. Five KIF5A mutations were identified in 6 unrelated patients: R204W and D232N were novel mutations; R204Q, R280C, and R280H have been previously reported. Three patients had CMT2 as the predominant and presenting phenotype; 2 of them also had pyramidal signs. The other 3 patients presented with HSP but also had significant axonal neuropathy or other additional features. This is currently the largest study investigating KIF5A mutations. By combining next-generation sequencing and conventional sequencing, we confirm that KIF5A mutations can cause variable phenotypes ranging from HSP to CMT2. The identification of mutations in CMT2 broadens the phenotypic spectrum and underlines the importance of KIF5A mutations, which involve degeneration of both the central and peripheral nervous systems and should be tested in HSP and CMT2.

Original languageEnglish
Pages (from-to)612-619
Number of pages8
JournalNeurology
Volume83
Issue number7
DOIs
StatePublished - Jan 1 2014

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Charcot-Marie-Tooth Disease
Paraplegia
Hereditary Spastic Paraplegia
Mutation
Exons
Exome
Phenotype
Peripheral Nervous System
Teeth
Central Nervous System
Sequencing

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

Cite this

Liu, Y. T., Laurá, M., Hersheson, J., Horga, A., Jaunmuktane, Z., Brandner, S., ... Houlden, H. (2014). Extended phenotypic spectrum of KIF5A mutations: From spastic paraplegia to axonal neuropathy. Neurology, 83(7), 612-619. https://doi.org/10.1212/WNL.0000000000000691

Extended phenotypic spectrum of KIF5A mutations : From spastic paraplegia to axonal neuropathy. / Liu, Yo Tsen; Laurá, Matilde; Hersheson, Joshua; Horga, Alejandro; Jaunmuktane, Zane; Brandner, Sebastian; Pittman, Alan; Hughes, Deborah; Polke, James M.; Sweeney, Mary G.; Proukakis, Christos; Janssen, John C.; Auer-Grumbach, Michaela; Zuchner, Stephan L; Shields, Kevin G.; Reilly, Mary M.; Houlden, Henry.

In: Neurology, Vol. 83, No. 7, 01.01.2014, p. 612-619.

Research output: Contribution to journalArticle

Liu, YT, Laurá, M, Hersheson, J, Horga, A, Jaunmuktane, Z, Brandner, S, Pittman, A, Hughes, D, Polke, JM, Sweeney, MG, Proukakis, C, Janssen, JC, Auer-Grumbach, M, Zuchner, SL, Shields, KG, Reilly, MM & Houlden, H 2014, 'Extended phenotypic spectrum of KIF5A mutations: From spastic paraplegia to axonal neuropathy.', Neurology, vol. 83, no. 7, pp. 612-619. https://doi.org/10.1212/WNL.0000000000000691
Liu YT, Laurá M, Hersheson J, Horga A, Jaunmuktane Z, Brandner S et al. Extended phenotypic spectrum of KIF5A mutations: From spastic paraplegia to axonal neuropathy. Neurology. 2014 Jan 1;83(7):612-619. https://doi.org/10.1212/WNL.0000000000000691
Liu, Yo Tsen ; Laurá, Matilde ; Hersheson, Joshua ; Horga, Alejandro ; Jaunmuktane, Zane ; Brandner, Sebastian ; Pittman, Alan ; Hughes, Deborah ; Polke, James M. ; Sweeney, Mary G. ; Proukakis, Christos ; Janssen, John C. ; Auer-Grumbach, Michaela ; Zuchner, Stephan L ; Shields, Kevin G. ; Reilly, Mary M. ; Houlden, Henry. / Extended phenotypic spectrum of KIF5A mutations : From spastic paraplegia to axonal neuropathy. In: Neurology. 2014 ; Vol. 83, No. 7. pp. 612-619.
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