TY - JOUR
T1 - Proof of a non-functional muscle chloride channel in recessive myotonia congenita (becker) by detection of a 4 base pair deletion
AU - Heine, Ronald
AU - George, Alfred L.
AU - Pika, Ursula
AU - Deymeer, Feza
AU - Rüdel, Reinhardt
AU - Lehmann-horn, Frank
N1 - Funding Information:
We are grateful to Drs C.Fahlke, E.P.Hoffman, C.TMzdemir and K.Ricker for helpful discussions and Ms S.Plate for secretarial help. We thank the families whose participation made this study possible. The work was supported by the Deutsche Forschungsgemeinschaft (Le 481/3-2).
PY - 1994/7
Y1 - 1994/7
N2 - 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.
AB - 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.
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U2 - 10.1093/hmg/3.7.1123
DO - 10.1093/hmg/3.7.1123
M3 - Article
C2 - 7981681
AN - SCOPUS:0028287533
VL - 3
SP - 1123
EP - 1128
JO - Human Molecular Genetics
JF - Human Molecular Genetics
SN - 0964-6906
IS - 7
ER -