Ronald Heine, Alfred L. George, Jr, Ursula Pika, Feza Deymeer, Reinhardt Rüdel, Frank Lehmann-Horn; Proof of a non-functional muscle chloride channel in recessive myotonia congenita (Becker) by detection of a 4 base pair deletion. Hum Mol Genet 1994; 3 (7): 1123-1128. doi: 10.1093/hmg/3.7.1123
Recessive myotonia congenlta (Becker) is genetically linked to HUMCLC, the gene encoding the muscular chloride channel, localized on chromosome 7q35. Three point mutations have so far been reported In HUMCLC, one causing recessive Becker-type myotonia, the others causing the clinically similar Thomsen-type myotonia, which is Inherited as a dominant trait. We report a homozygous patient having a 4 base pair deletion in HUMCLC that shifts the reading frame and causes early stop codons, thus destroying the gene's coding potential for several membrane-spanning domains. In addition, we report a patient homozygous for a novel point mutation located at the extracellular side of the first membrane-spanning domain that causes removal of a negative charge (aspartic acid-136-glyclne). Both mutations lead to the recessive type of myotonia congenita. Since the patient having the deletion presents less severe clinical myotonia than the patient carrying the missense mutation, it seems that the absence or truncation of the channel protein may disturb muscle fibre function less than the substitution of a single amino acid.