Rethink of KIF1A HSP mutation

Posted - February 2015 in Research Highlights

Not just recessive complicated HSP

 .

This collaborative Finnish–Korean study of the KIF1A gene has found that it is not only responsible for a complicated form of HSP passed on by recessive inheritance, but also for pure HSP transmitted by dominant inheritance. This means that the KIF1A gene should be included in testing no matter what the form or inheritance of HSP is in any particular case.

.

Variants in family 1 kinesin (KIF1A), which encodes a kinesin axonal motor protein, have been described to cause variable neurological manifestations. Recessive missense variants have led to spastic paraplegia, and recessive truncations to sensory and autonomic neuropathy. De novo missense variants cause developmental delay or intellectual disability, cerebellar atrophy and variable spasticity.

We describe a family with father-to-son transmission of a de novo variant in the KIF1A motor domain, in a phenotype of pure spastic paraplegia. Structural modeling of the predicted p.(Ser69Leu) amino acid change suggested that it impairs the stable binding of ATP to the KIF1A protein. Our study reports the first dominantly inherited KIF1A variant and expands the spectrum of phenotypes caused by heterozygous KIF1A motor domain variants to include pure spastic paraplegia.

We conclude that KIF1A should be considered a candidate gene for hereditary paraplegias regardless of inheritance pattern.

SOURCE: Eur J Hum Genet. 2015 Jan 14. doi: 10.1038/ejhg.2014.297. [Epub ahead of print] PMID: 25585697  [PubMed – as supplied by publisher]

Dominant transmission of de novo KIF1A motor domain variant underlying pure spastic paraplegia.

Ylikallio E1, Kim D2, Isohanni P3, Auranen M4, Kim E5, Lönnqvist T6, Tyynismaa H7.

  • 1Research Programs Unit, Molecular Neurology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.

  • 2Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS), Daejeon, Korea.

  • 31] Research Programs Unit, Molecular Neurology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland [2] Department of Child Neurology, Children’s Hospital, Helsinki University Central Hospital, Helsinki, Finland.

  • 41] Research Programs Unit, Molecular Neurology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland [2] Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland.

  • 51] Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS), Daejeon, Korea [2] Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.

  • 6Department of Child Neurology, Children’s Hospital, Helsinki University Central Hospital, Helsinki, Finland.

  • 71] Research Programs Unit, Molecular Neurology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland [2] Department of Medical Genetics, Haartman Institute, University of Helsinki, Helsinki, Finland.

Add your comment on this story