title: A novel N440K sodium channel mutation causes myotonia with exercise-induced weakness--exclusion of CLCN1 exon deletion/duplication by MLPA.
abstract: We report a 4-generation Turkish family with 10 affected members presenting with myotonia and potassium- and exercise-induced paralytic attacks. The clinical presentation was neither typical for the chloride channel myotonias Thomsen and Becker nor for the separate sodium channel myotonia entities potassium-aggravated myotonia, paramyotonia congenita, and hyperkalemic periodic paralysis. It is best described by a combination of potassium-aggravated myotonia and hyperkalemic periodic paralysis. We excluded exonic chloride channel mutations including CLCN1 exon deletion/duplication by MLPA. Instead we identified a novel p.N440K sodium channel mutation that is located at the inner end of segment S6 of repeat I. We discuss the genotype phenotype relation.
authors: Division of Neurophysiology, Ulm University, Ulm, Germany. frank.lehmann-horn@uni-ulm.de
authors: F
authors: F
authors: Lehmann-Horn
authors: M
authors: M
authors: Orth
authors: M
authors: M
authors: Kuhn
authors: K
authors: K
authors: Jurkat-Rott
mesh_terms: D000086:Acetazolamide / Q000627:therapeutic use; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D000927:Anticonvulsants / Q000627:therapeutic use; D018118:Chloride Channels / Q000235:genetics*; D006801:Humans; D006947:Hyperkalemia / Q000150:complications*; D006948:Hyperkinesis / Q000150:complications* / Q000503:physiopathology; D018908:Muscle Weakness / Q000209:etiology / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000503:physiopathology; D009224:Myotonia Congenita / Q000188:drug therapy / Q000209:etiology / Q000235:genetics*; D010243:Paralysis / Q000209:etiology / Q000503:physiopathology; D010375:Pedigree; D056916:Segmental Duplications, Genomic; D017384:Sequence Deletion; D012720:Severity of Illness Index; D015222:Sodium Channels / Q000235:genetics*
chemical_list: D000889:Anti-Arrhythmia Agents; D000927:Anticonvulsants; C086321:CLC-1 channel; D018118:Chloride Channels; D015222:Sodium Channels; D000086:Acetazolamide