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From the Medical Research Council Centre for Neuromuscular Disease, Department of Molecular Neuroscience, Institute of Neurology and National Hospital for Neurology and Neurosurgery, London, UK.
Address correspondence and reprint requests to Dr Hanna, Medical Research Council Centre for Neuromuscular Disease, Department of Molecular Neuroscience, Institute of Neurology and National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK m.hanna{at}ion.ucl.ac.uk
Objective: To study the clinical and genetic features in a large cohort of UK patients with sodium channel paramyotonia congenita.
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.
GLOSSARY: ADM = abductor digiti minimi; CMAP = compound motor action potential; hyper-PP/PMC = paramyotonia congenita with periodic paralysis; MF = myotonia fluctuans; MP = myotonia permanens; PAM = potassium-aggravated myotonia; PMC = paramyotonia congenita.
Supplemental data at www.neurology.org
Supported by the Medical Research Council UK and NIH through the NIH–Consortium for Clinical Investigation of Neurologic Channelopathies (NIH grant no. 1 U45 RR198442-01). This work was undertaken at University College London Hospitals/University College London, which received a proportion of funding from the Department of Health’s National Institute for Health Research Biomedical Research Centres funding scheme.
Disclosure: The authors report no conflicts of interest.
Received November 28, 2006. Accepted in final form June 20, 2007.
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