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.
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.
Authors: Véronique Bissay; Sophie C H Van Malderen; Kathelijn Keymolen; Willy Lissens; Uschi Peeters; Dorien Daneels; Anna C Jansen; Gudrun Pappaert; Pedro Brugada; Jacques De Keyser; Sonia Van Dooren Journal: Eur J Hum Genet Date: 2015-06-03 Impact factor: 4.246
Authors: Bas C Stunnenberg; Samantha LoRusso; W David Arnold; Richard J Barohn; Stephen C Cannon; Bertrand Fontaine; Robert C Griggs; Michael G Hanna; Emma Matthews; Giovanni Meola; Valeria A Sansone; Jaya R Trivedi; Baziel G M van Engelen; Savine Vicart; Jeffrey M Statland Journal: Muscle Nerve Date: 2020-05-27 Impact factor: 3.217
Authors: Emma Matthews; James A L Miller; Malcolm R MacLeod; James Ironside; Gareth Ambler; Robin Labrum; Richa Sud; Janice L Holton; Michael G Hanna Journal: Muscle Nerve Date: 2011-06-22 Impact factor: 3.217
Authors: S Rajakulendran; S V Tan; E Matthews; S E Tomlinson; R Labrum; R Sud; D M Kullmann; S Schorge; M G Hanna Journal: Neurology Date: 2009-09-22 Impact factor: 9.910