Heterozygous mutation in the pore of potassium channel gene KvLQT1 causes an apparently normal phenotype in long QT syndrome.
Mutations in KvLQT1, a gene encoding a potassium channel, cause both the recessive Jervell and Lange-Nielsen (JLN) syndrome and the dominant Romano-Ward (RW) syndrome. These diseases are characterised by a prolonged QT interval on the ECG, syncopes and sudden death due to cardiac arrhythmias. The JLN syndrome is also associated with a congenital bilateral deafness. We report here a novel missense mutation, W305S, in the pore region of KvLQT1 identified by PCR-SSCP analysis in two consanguineous JLN families. In contrast to several missense mutations found in the same region of KvLQT1 in RW patients which are associated with severe cardiac phenotypes, the W305S mutation is responsible for an apparently normal phenotype in heterozygous JLN carriers.
Neyroud
N
N
INSERM UR153, Groupe Hospitalier Pitié-Salpêtrière, Institut de Myologie, Paris, France. nneyroud@myologie.infobiogen.fr
Denjoy
I
I
Donger
C
C
Gary
F
F
Villain
E
E
Leenhardt
A
A
Benali
K
K
Schwartz
K
K
Coumel
P
P
Guicheney
P
P
D003241:Consanguinity; D005260:Female; D006579:Heterozygote; D006801:Humans; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D008133:Long QT Syndrome / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D015221:Potassium Channels / Q000235:genetics*; D024642:Potassium Channels, Voltage-Gated
D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated