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), 2251-2255. (doi:10.1038/eye.2008.389).
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Description/Abstract
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
| Item Type: | Article |
|---|---|
| ISSNs: | 0950-222X (print) |
| Related URLs: | |
| Keywords: | nystagmus, CACNA1A, ataxia, gene, mutation, infantile |
| Subjects: | Q Science > QH Natural history > QH426 Genetics |
| Divisions: | University Structure - Pre August 2011 > School of Medicine > Clinical Neurosciences University Structure - Pre August 2011 > School of Medicine > Human Genetics |
| Item ID: | 72443 |
| Date Deposited: | 15 Feb 2010 |
| Last Modified: | 23 Jul 2012 00:41 |
| Contributors: | Self, J. (Author) Mercer, C. (Author) Boon, E.M. (Author) Murugavel, M. (Author) Shawkat, F. (Author) Hammans, S. (Author) Hodgkins, P. (Author) Griffiths, H. (Author) Lotery, A. (Author) |
| Date: | December 2009 |
| Status: | Published |
| URI: | http://eprints.soton.ac.uk/id/eprint/72443 |
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