title: Novel CACNA1A mutation(s) associated with slow saccade velocities.
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.
authors.affiliation: Perception and Eye Movement Laboratory, Departments of Clinical Research and Neurology, Inselspital, Bern University Hospital, and University of Bern, Freiburgstrasse 10, 3010, Bern, Switzerland, s.kipfer@gmx.ch.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kipfer
authors.forename: Simon
authors.initials: S
authors.lastname: Jung
authors.forename: Johannes R
authors.initials: JR
authors.lastname: Lemke
authors.forename: Anna
authors.initials: A
authors.lastname: Kipfer-Kauer
authors.forename: Jeremy P
authors.initials: JP
authors.lastname: Howell
authors.forename: Alain
authors.initials: A
authors.lastname: Kaelin-Lang
authors.forename: Thomas
authors.initials: T
authors.lastname: Nyffeler
authors.forename: Klemens
authors.initials: K
authors.lastname: Gutbrod
authors.forename: Angela
authors.initials: A
authors.lastname: Abicht
authors.forename: René M
authors.initials: RM
authors.lastname: Müri
mesh_terms: D001259:Ataxia / Q000235:genetics*; D015220:Calcium Channels / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D009154:Mutation; D009759:Nystagmus, Pathologic / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D012438:Saccades / Q000235:genetics*; D055815:Young Adult; D020864:Calcium Channels, N-Type
chemical_list: D015220:Calcium Channels; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type
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