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Abstract
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.
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