Self, J., Mercer, C., Boon, E.M., Murugavel, M., Shawkat, F., Hammans, S., Hodgkins, P., Griffiths, H. and Lotery, A.
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), . (doi:10.1038/eye.2008.389).
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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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