Infantile nystagmus and late onset ataxia associated with a CACNA1A mutation in the intracellular loop between s4 and s5 of domain 3
Infantile nystagmus and late onset ataxia associated with a CACNA1A mutation in the intracellular loop between s4 and s5 of domain 3
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
nystagmus, CACNA1A, ataxia, gene, mutation, infantile
2251-2255
Self, J.
0f6efc58-ae24-4667-b8d6-6fafa849e389
Mercer, C.
5889a50a-0e0b-49cd-94d0-4184c5f303d0
Boon, E.M.
25fd826d-5736-4b9e-8cca-d48814801b9b
Murugavel, M.
2792b59a-07c9-481c-aff3-db1e5a7182e5
Shawkat, F.
580315b7-94dd-4606-a311-5f58b1988cda
Hammans, S.
6553eac5-9322-4f2b-b677-d4ba698fc10b
Hodgkins, P.
1124e3a7-465a-49e1-8dff-259c5d07bc69
Griffiths, H.
70eb2bea-383a-4a10-bd01-826bc07f1a11
Lotery, A.
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
December 2009
Self, J.
0f6efc58-ae24-4667-b8d6-6fafa849e389
Mercer, C.
5889a50a-0e0b-49cd-94d0-4184c5f303d0
Boon, E.M.
25fd826d-5736-4b9e-8cca-d48814801b9b
Murugavel, M.
2792b59a-07c9-481c-aff3-db1e5a7182e5
Shawkat, F.
580315b7-94dd-4606-a311-5f58b1988cda
Hammans, S.
6553eac5-9322-4f2b-b677-d4ba698fc10b
Hodgkins, P.
1124e3a7-465a-49e1-8dff-259c5d07bc69
Griffiths, H.
70eb2bea-383a-4a10-bd01-826bc07f1a11
Lotery, A.
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
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), .
(doi:10.1038/eye.2008.389).
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
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Published date: December 2009
Keywords:
nystagmus, CACNA1A, ataxia, gene, mutation, infantile
Organisations:
Human Genetics, Clinical Neurosciences
Identifiers
Local EPrints ID: 72443
URI: http://eprints.soton.ac.uk/id/eprint/72443
ISSN: 0950-222X
PURE UUID: 38f30a34-4034-496b-8007-1ff11575ff8c
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Date deposited: 15 Feb 2010
Last modified: 14 Mar 2024 02:50
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Contributors
Author:
C. Mercer
Author:
E.M. Boon
Author:
M. Murugavel
Author:
F. Shawkat
Author:
S. Hammans
Author:
P. Hodgkins
Author:
H. Griffiths
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