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Infantile nystagmus and late onset ataxia associated with a CACNA1A mutation in the intracellular loop between s4 and s5 of domain 3

Self, J., Mercer, C., Boon, E.M., Murugavel, M., Shawkat, F., Hammans, S., Hodgkins, P., Griffiths, H. and Lotery, A. (2009) Infantile nystagmus and late onset ataxia associated with a CACNA1A mutation in the intracellular loop between s4 and s5 of domain 3 Eye, 23, (12), pp. 2251-2255. (doi:10.1038/eye.2008.389).

Record type: Article


Purpose: mutations in the 1A-subunit of the brain P/Q-type calcium channel gene CACNA1Aare responsible for spinocerebellar ataxia type 6 (SCA6), familial haemiplegic migraine (FHM) and episodic ataxia type 2 (EA2). Considerable clinical and genetic overlap exists between these 3 allelic disorders. Clinical findings are varied and may include nystagmus.

Objective: to study the clinical phenotype and identify a causative mutation in a family who presented when the youngest member was diagnosed with apparent isolated congenital nystagmus (age 3 months).

Patients and Methods: 8 patients from one family underwent detailed clinical phenotyping comprising; ophthalmic and neurological examination, nystagmology, electrodiagnostic tests and brain imaging. The CACNA1Agene was screened for mutations by direct sequencing in one patient. Co-segregation of the disease and an identified sequence variation was shown using direct sequencing.

Results: phenotyping revealed isolated atypical nystagmus in 4 family members and nystagmus in addition to late onset ataxia in 1 family member. Direct sequencing of the CACNA1Agene identified a novel missense mutation; (c.4110T>G p.Phe1370Leu (NM_000068.3)).

Conclusions: we have shown that a mutation in the intracellular domain between s4 and s5 of repeat 3 can cause atypical nystagmus/cerebellar phenotypes, including isolated nystagmus in an infant. We also illustrate the necessity for detailed examination of relatives in cases of apparent isolated congenital nystagmus

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Published date: December 2009
Keywords: nystagmus, CACNA1A, ataxia, gene, mutation, infantile
Organisations: Human Genetics, Clinical Neurosciences


Local EPrints ID: 72443
ISSN: 0950-222X
PURE UUID: 38f30a34-4034-496b-8007-1ff11575ff8c
ORCID for J. Self: ORCID iD

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Date deposited: 15 Feb 2010
Last modified: 18 Jul 2017 23:54

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Author: J. Self ORCID iD
Author: C. Mercer
Author: E.M. Boon
Author: M. Murugavel
Author: F. Shawkat
Author: S. Hammans
Author: P. Hodgkins
Author: H. Griffiths
Author: A. Lotery

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