PMID- 10590249
OWN - NLM
STAT- MEDLINE
DCOM- 20000104
LR  - 20190706
IS  - 0009-7330 (Print)
IS  - 0009-7330 (Linking)
VI  - 85
IP  - 12
DP  - 1999 Dec 3-17
TI  - A single Na(+) channel mutation causing both long-QT and Brugada syndromes.
PG  - 1206-13
AB  - Mutations in SCN5A, the gene encoding the cardiac Na(+) channel, have been
      identified in 2 distinct diseases associated with sudden death: one form of the
      long-QT syndrome (LQT(3)) and the Brugada syndrome. We have screened SCN5A in a
      large 8-generation kindred characterized by a high incidence of nocturnal sudden 
      death, and QT-interval prolongation and the "Brugada ECG" occurring in the same
      subjects. An insertion of 3 nucleotides (TGA) at position 5537, predicted to
      cause an insertion of aspartic acid (1795insD) in the C-terminal domain of the
      protein, was linked to the phenotype and was identified in all
      electrocardiographically affected family members. ECGs were obtained from 79
      adults with a defined genetic status (carriers, n=43; noncarriers, n=36). In
      affected individuals, PR and QRS durations and QT intervals are prolonged
      (P<0.0001 for all parameters). ST segment elevation in the right precordial leads
      is present as well (P<0.0001). Twenty-five family members died suddenly, 16 of
      them during the night. Expression of wild-type and mutant Na(+) channels in
      Xenopus oocytes revealed that the 1795insD mutation gives rise to a 7.3-mV
      negative shift of the steady-state inactivation curve and an 8.1-mV positive
      shift of the steady-state activation curve. The functional consequence of both
      shifts is likely to be a reduced Na(+) current during the upstroke of the action 
      potential. LQT(3) and Brugada syndrome are allelic disorders but may also share a
      common genotype.
FAU - Bezzina, C
AU  - Bezzina C
AD  - Departments of Clinical Genetics , Academic Medical Center, Amsterdam, The
      Netherlands.
FAU - Veldkamp, M W
AU  - Veldkamp MW
FAU - van Den Berg, M P
AU  - van Den Berg MP
FAU - Postma, A V
AU  - Postma AV
FAU - Rook, M B
AU  - Rook MB
FAU - Viersma, J W
AU  - Viersma JW
FAU - van Langen, I M
AU  - van Langen IM
FAU - Tan-Sindhunata, G
AU  - Tan-Sindhunata G
FAU - Bink-Boelkens, M T
AU  - Bink-Boelkens MT
FAU - van Der Hout, A H
AU  - van Der Hout AH
FAU - Mannens, M M
AU  - Mannens MM
FAU - Wilde, A A
AU  - Wilde AA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (Sodium Channels)
SB  - IM
MH  - Adult
MH  - Death, Sudden, Cardiac/*etiology
MH  - Electrocardiography
MH  - Female
MH  - Humans
MH  - Long QT Syndrome/*etiology/*genetics
MH  - Male
MH  - *Mutation
MH  - Pedigree
MH  - Sodium Channels/*genetics
EDAT- 1999/12/11 00:00
MHDA- 1999/12/11 00:01
CRDT- 1999/12/11 00:00
PHST- 1999/12/11 00:00 [pubmed]
PHST- 1999/12/11 00:01 [medline]
PHST- 1999/12/11 00:00 [entrez]
AID - 10.1161/01.res.85.12.1206 [doi]
PST - ppublish
SO  - Circ Res. 1999 Dec 3-17;85(12):1206-13. doi: 10.1161/01.res.85.12.1206.