Motor protein mutations cause a new form of hereditary spastic paraplegia

Andrés Caballero Oteyza, Esra Battaloǧlu, Levent Ocek, Tobias Lindig, Jennifer Reichbauer, Adriana P. Rebelo, Michael A. Gonzalez, Yasar Zorlu, Burcak Ozes, Dagmar Timmann, Benjamin Bender, Günther Woehlke, Stephan Züchner, Ludger Schöls, Rebecca Schüle

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Objective: To identify a novel disease gene in 2 families with autosomal recessive hereditary spastic paraplegia (HSP). Methods: We used whole-exome sequencing to identify the underlying genetic disease cause in 2 families with apparently autosomal recessive spastic paraplegia. Endogenous expression as well as subcellular localization of wild-type and mutant protein were studied to support the pathogenicity of the identified mutations. Results: In 2 families, we identified compound heterozygous or homozygous mutations in the kinesin gene KIF1C to cause hereditary spastic paraplegia type 58 (SPG58). SPG58 can be complicated by cervical dystonia and cerebellar ataxia. The same mutations in a heterozygous state result in a mild or subclinical phenotype. KIF1C mutations in SPG58 affect the domains involved in adenosine triphosphate hydrolysis and microtubule binding, key functions for this microtubule-based motor protein. Conclusions: KIF1C is the third kinesin gene involved in the pathogenesis of HSPs and is characterized by a mild dominant and a more severe recessive disease phenotype. The identification of KIF1C as an HSP disease gene further supports the key role of intracellular trafficking processes in the pathogenesis of hereditary axonopathies.

Original languageEnglish (US)
Pages (from-to)2007-2016
Number of pages10
Issue number22
StatePublished - Jun 3 2014

ASJC Scopus subject areas

  • Clinical Neurology


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