Abstract | OBJECTIVE: METHODS: We conducted a UK-wide clinical and molecular genetic study of patients presenting with a phenotype suggestive of paramyotonia congenita. RESULTS: We identified 42 affected individuals (28 kindreds). All cases met our core criteria for a clinical diagnosis of paramyotonia congenita. Seventy-five percent of patients (32 patients/20 kindreds) had SCN4A mutations. Twenty-nine subjects from 18 kindreds had exon 22 and 24 mutations, confirming these exons to be hot spots. Unexpectedly, 3 of these subjects harbored mutations previously described with potassium-aggravated myotonia (G1306A, G1306E). We identified two new mutations (R1448L and L1436P). Ten cases (8 kindreds) without mutations exhibited paramyotonia congenita with prominent pain and weakness. CONCLUSIONS: This study identifies two new mutations, confirms SCN4A as a common cause of paramyotonia congenita in the UK, and suggests further allelic and possibly genetic heterogeneity.
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Authors | E Matthews, S V Tan, D Fialho, M G Sweeney, R Sud, A Haworth, E Stanley, G Cea, M B Davis, M G Hanna |
Journal | Neurology
(Neurology)
Vol. 70
Issue 1
Pg. 50-3
(Jan 01 2008)
ISSN: 1526-632X [Electronic] United States |
PMID | 18166706
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- NAV1.4 Voltage-Gated Sodium Channel
- SCN4A protein, human
- Sodium Channels
- Arginine
- Proline
- Leucine
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Topics |
- Action Potentials
(physiology)
- Arginine
(genetics)
- Cohort Studies
- Exons
(genetics)
- Female
- Humans
- Leucine
(genetics)
- Male
- Mutation
- Myotonic Disorders
(epidemiology, genetics, physiopathology)
- NAV1.4 Voltage-Gated Sodium Channel
- Neural Conduction
(physiology)
- Proline
(genetics)
- Sodium Channels
(genetics)
- United Kingdom
(epidemiology, ethnology)
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