PMID- 10220144
OWN - NLM
STAT- MEDLINE
DCOM- 19990610
LR  - 20161124
IS  - 1059-7794 (Print)
IS  - 1059-7794 (Linking)
VI  - 13
IP  - 4
DP  - 1999
TI  - Novel KCNQ1 and HERG missense mutations in Dutch long-QT families.
PG  - 301-10
AB  - Congenital long QT syndrome (cLQTS) is electrocardiographically characterized by 
      a prolonged QT interval and polymorphic ventricular arrhythmias (torsade de
      pointes). These cardiac arrhythmias may result in recurrent syncopes, seizure, or
      sudden death. LQTS can occur either as an autosomal dominant (Romano Ward) or as 
      an autosomal recessive disorder (Jervell and Lange-Nielsen syndrome). Mutations
      in at least five genes have been associated with the LQTS. Four genes, encoding
      cardiac ion channels, have been identified. The most common forms of LQTS are due
      to mutations in the potassium-channel genes KCNQ1 and HERG. We have screened 24
      Dutch LQTS families for mutations in KCNQ1 and HERG. Fourteen missense mutations 
      were identified. Eight of these missense mutations were novel: three in KCNQ1 and
      five in HERG. Novel missense mutations in KCNQ1 were Y184S, S373P, and W392R and 
      novel missense mutations in HERG were A558P, R582C, G604S, T613M, and F640L. The 
      KCNQ1 mutation G189R and the HERG mutation R582C were detected in two families.
      The pathogenicity of the mutations was based on segregation in families, absence 
      in control individuals, the nature of the amino acid substitution, and
      localization in the protein. Genotype-phenotype studies indicated that auditory
      stimuli as trigger of cardiac events differentiate LQTS2 and LQTS1. In LQTS1,
      exercise was the predominant trigger. In addition, a number of asymptomatic gene 
      defect carriers were identified. Asymptomatic carriers are still at risk of the
      development of life-threatening arrhythmias, underlining the importance of DNA
      analyses for unequivocal diagnosis of patients with LQTS.
FAU - Jongbloed, R J
AU  - Jongbloed RJ
AD  - Department of Molecular Cell Biology and Genetics, Cardiovascular Research
      Institute Maastricht, University of Maastricht, The Netherlands.
      roselie.jongbloed@gen.unimas.nl
FAU - Wilde, A A
AU  - Wilde AA
FAU - Geelen, J L
AU  - Geelen JL
FAU - Doevendans, P
AU  - Doevendans P
FAU - Schaap, C
AU  - Schaap C
FAU - Van Langen, I
AU  - Van Langen I
FAU - van Tintelen, J P
AU  - van Tintelen JP
FAU - Cobben, J M
AU  - Cobben JM
FAU - Beaufort-Krol, G C
AU  - Beaufort-Krol GC
FAU - Geraedts, J P
AU  - Geraedts JP
FAU - Smeets, H J
AU  - Smeets HJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hum Mutat
JT  - Human mutation
JID - 9215429
RN  - 0 (Cation Transport Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (ERG protein, human)
RN  - 0 (ERG1 Potassium Channel)
RN  - 0 (Ether-A-Go-Go Potassium Channels)
RN  - 0 (KCNH2 protein, human)
RN  - 0 (KCNH6 protein, human)
RN  - 0 (KCNQ Potassium Channels)
RN  - 0 (KCNQ1 Potassium Channel)
RN  - 0 (KCNQ1 protein, human)
RN  - 0 (Potassium Channels)
RN  - 0 (Potassium Channels, Voltage-Gated)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcriptional Regulator ERG)
SB  - IM
MH  - *Cation Transport Proteins
MH  - DNA Mutational Analysis
MH  - *DNA-Binding Proteins
MH  - ERG1 Potassium Channel
MH  - Ether-A-Go-Go Potassium Channels
MH  - Genetic Linkage
MH  - Haplotypes
MH  - Humans
MH  - KCNQ Potassium Channels
MH  - KCNQ1 Potassium Channel
MH  - Long QT Syndrome/*genetics
MH  - Microsatellite Repeats
MH  - *Mutation, Missense
MH  - Netherlands
MH  - Pedigree
MH  - Polymorphism, Genetic
MH  - Potassium Channels/*genetics
MH  - *Potassium Channels, Voltage-Gated
MH  - Sequence Homology, Amino Acid
MH  - *Trans-Activators
MH  - Transcriptional Regulator ERG
EDAT- 1999/04/29 02:03
MHDA- 2000/06/22 10:00
CRDT- 1999/04/29 02:03
PHST- 1999/04/29 02:03 [pubmed]
PHST- 2000/06/22 10:00 [medline]
PHST- 1999/04/29 02:03 [entrez]
AID - 10.1002/(SICI)1098-1004(1999)13:4<301::AID-HUMU7>3.0.CO;2-V [pii]
AID - 10.1002/(SICI)1098-1004(1999)13:4<301::AID-HUMU7>3.0.CO;2-V [doi]
PST - ppublish
SO  - Hum Mutat. 1999;13(4):301-10. doi:
      10.1002/(SICI)1098-1004(1999)13:4<301::AID-HUMU7>3.0.CO;2-V.