Journal of Neurology

, Volume 260, Issue 12, pp 3010–3014

Novel CACNA1A mutation(s) associated with slow saccade velocities

  • Stefan Kipfer
  • Simon Jung
  • Johannes R. Lemke
  • Anna Kipfer-Kauer
  • Jeremy P. Howell
  • Alain Kaelin-Lang
  • Thomas Nyffeler
  • Klemens Gutbrod
  • Angela Abicht
  • René M. Müri
Original Communication

Abstract

Mutations in the voltage-gated Cav2.1 P/Q-type calcium channel (CACNA1A) can cause a wide spectrum of phenotypes, including the episodic ataxia type 2. Beside the growing number of descriptions of novel CACNA1A mutations with episodic ataxia type 2 phenotype; there are only rare reports on interictal oculomotor signs other than nystagmus. We describe a novel CACNA1A mutation and an unclassified CACNA1A in-frame variant in a Swiss family presenting as the episodic ataxia type 2 phenotype associated with reduced saccade velocity. In this case series interictal clinical examination showed only minimal neurological findings as mild limb ataxia and nystagmus, but most interestingly saccade analysis of all three affected individuals demonstrated reduced mean saccade velocity. Genetic testing of CACNA1A revealed a de novo frame-shift mutation (c.2691dupC/p.Thyr898Leufs*170) in the index patient in addition to an unclassified in-frame variant (c.6657_6659dupCCA/p.His2220dup) segregating in all three affected individuals. The de novo frame-shift CACNA1A mutation and the unclassified in-frame CACNA1A variant were associated with the episodic ataxia type 2 phenotype and reduced mean saccade velocity, which suggests involvement of brainstem or neural pathways connecting brainstem and the cerebellum in this disease.

Keywords

Episodic ataxia type 2 CACNA1 mutation Saccadic eye movements Nystagmus 

Supplementary material

Neuro-ophthalmologic core features of proband 1 (index patient) (MOV 4920 kb)

415_2013_7099_MOESM2_ESM.tif (3.5 mb)
Raw eye movement traces of proband 1 (index patient) showing horizontal saccades of both eyes (TIFF 3616 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Stefan Kipfer
    • 1
    • 2
  • Simon Jung
    • 1
  • Johannes R. Lemke
    • 3
  • Anna Kipfer-Kauer
    • 4
  • Jeremy P. Howell
    • 4
  • Alain Kaelin-Lang
    • 5
  • Thomas Nyffeler
    • 1
  • Klemens Gutbrod
    • 1
  • Angela Abicht
    • 6
  • René M. Müri
    • 1
  1. 1.Perception and Eye Movement Laboratory, Departments of Clinical Research and NeurologyInselspital, Bern University Hospital, and University of BernBernSwitzerland
  2. 2.Department of NeurologyKantonsspital OltenOltenSwitzerland
  3. 3.Division of Human GeneticsInselspital, University of Bern Children’s HospitalBernSwitzerland
  4. 4.Department of OphthalmologyKantonsspital LuzernLuzern 16Switzerland
  5. 5.Department of Neurology, Movement Disorders CenterInselspital, Bern University Hospital, and University of BernBernSwitzerland
  6. 6.Medical Genetics Center (MGZ)MunichGermany

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