We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
In tandem analysis of CLCN1 and SCN4A greatly enhances mutation detection in families with non-dystrophic myotonia.
- Authors
Trip, Jeroen; Drost, Gea; Verbove, Dennis J; van der Kooi, Anneke J; Kuks, Jan B M; Notermans, Nicolette C; Verschuuren, Jan J; de Visser, Marianne; van Engelen, Baziel G M; Faber, Carin G; Ginjaar, Ieke B
- Abstract
Non-dystrophic myotonias (NDMs) are caused by mutations in CLCN1 or SCN4A. The purpose of the present study was to optimize the genetic characterization of NDM in The Netherlands by analysing CLCN1 and SCN4A in tandem. All Dutch consultant neurologists and the Dutch Patient Association for Neuromuscular Diseases (Vereniging Spierziekten Nederland) were requested to refer patients with an initial diagnosis of NDM for clinical assessment and subsequent genetic analysis over a full year. Based on clinical criteria, sequencing of either CLCN1 or SCN4A was performed. When previously described mutations or novel mutations were identified in the first gene under study, the second gene was not sequenced. If no mutations were detected in the first gene, the second gene was subsequently also analysed. Underlying NDM mutations were explored in 54 families. In total, 20% (8 of 40) of our probands with suspected chloride channel myotonia showed no CLCN1 mutations but subsequent SCN4A screening revealed mutations in all of them. All 14 probands in whom SCN4A was primarily sequenced showed a mutation. In total, CLCN1 mutations were identified in 32 families (59%) and SCN4A in 22 (41%), resulting in a diagnostic yield of 100%. The yield of mutation detection was 93% with three recessive and three sporadic cases not yielding a second mutation. Among these mutations, 13 in CLCN1 and 3 in SCN4A were novel. In conclusion, the current results show that in tandem analysis of CLCN1 and SCN4A affords high-level mutation ascertainment in families with NDM.European Journal of Human Genetics (2008) 16, 921–929; doi:10.1038/ejhg.2008.39; published online 12 March 2008
- Subjects
NETHERLANDS; MYOTONIA; GENETIC mutation; NEUROLOGICAL disorders; HUMAN genetics
- Publication
European Journal of Human Genetics, 2008, Vol 16, Issue 8, p921
- ISSN
1018-4813
- Publication type
Article
- DOI
10.1038/ejhg.2008.39