LAUSR

Myotonia congenita is a genetic disease of skeletal muscle membrane hyperexcitability caused by variants in CLCN1, leading to reduced conductance of the main skeletal muscle chloride channel (ClC-1) [1]. This disorder can be inherited in an autosomal dominant (Thomsen disease; sometimes associated with reduced penetrance) or recessive (Becker disease; OMIM 255700) fashion. Thomsen disease is rare and exhibits a high degree of genetic heterogeneity. The following variant types in CLCN1 have been reported: missense, nonsense, long deletions/duplications, insertions/deletions (indels), combined indels, and splice site [2]. The majority of Thomsen disease variants are missense [3] and a hotspot has been reported in exon 8, which codes for a region of interaction between ClC-1 monomers [4]. Over 200 CLCN1 variants have been identified as affecting chloride channel function (dominant and recessive inheritance), and a regularly updated database exists (available at: http://chromium. lovd.nl/LOVD2/variants.php?select_db= CLCN1&action= view_unique).