PMID- 10508990
OWN - NLM
STAT- MEDLINE
DCOM- 19991105
LR  - 20190905
IS  - 0148-7299 (Print)
IS  - 0148-7299 (Linking)
VI  - 86
IP  - 5
DP  - 1999 Oct 29
TI  - Sodium channel abnormalities are infrequent in patients with long QT syndrome:
      identification of two novel SCN5A mutations.
PG  - 470-6
AB  - Long QT syndrome (LQTS) is a heterogeneous disorder caused by mutations of at
      least five different loci. Three of these, LQT1, LQT2, and LQT5, encode potassium
      channel subunits. LQT3 encodes the cardiac-specific sodium channel, SCN5A.
      Previously reported LQTS-associated mutations of SCN5A include a recurring three 
      amino acid deletion (DeltaKPQ1505-1507) in four different families, and four
      different missense mutations. We have examined the SCN5A gene in 88 index cases
      with LQTS, including four with Jervell and Lange-Nielsen syndrome and the
      remainder with Romano-Ward syndrome. Screening portions of DIII-DIV, where
      mutations have previously been found, showed that none of these patients has the 
      three amino acid deletion, DeltaKPQ1505-1507, or the other four known mutations. 
      We identified a novel missense mutation, T1645M, in the DIV; S4 voltage sensor
      immediately adjacent to the previously reported mutation R1644H. We also examined
      all of the additional pore-forming regions and voltage-sensing regions and
      discovered another novel mutation, T1304M, at the voltage-sensing region DIII;
      S4. Neither T1645M nor T1304M were seen in a panel of unaffected control
      individuals. Five of six T1304M gene carriers were symptomatic. In contrast to
      previous studies, QT(onset-c) was not a sensitive indicator of SCN5A-associated
      LQTS, at least in this family. These data suggest that mutations of SCN5A are
      responsible for only a small proportion of LQTS cases.
CI  - Copyright 1999 Wiley-Liss, Inc.
FAU - Wattanasirichaigoon, D
AU  - Wattanasirichaigoon D
AD  - Division of Genetics, Children's Hospital, Boston, Massachusetts 02115, USA.
FAU - Vesely, M R
AU  - Vesely MR
FAU - Duggal, P
AU  - Duggal P
FAU - Levine, J C
AU  - Levine JC
FAU - Blume, E D
AU  - Blume ED
FAU - Wolff, G S
AU  - Wolff GS
FAU - Edwards, S B
AU  - Edwards SB
FAU - Beggs, A H
AU  - Beggs AH
LA  - eng
GR  - KO2 AR02026/AR/NIAMS NIH HHS/United States
GR  - R01 AR44345/AR/NIAMS NIH HHS/United States
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Med Genet
JT  - American journal of medical genetics
JID - 7708900
RN  - 0 (NAV1.5 Voltage-Gated Sodium Channel)
RN  - 0 (SCN5A protein, human)
RN  - 0 (Sodium Channels)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Amino Acid Substitution
MH  - Chromosome Mapping
MH  - Female
MH  - Genetic Variation
MH  - Humans
MH  - Long QT Syndrome/*genetics/physiopathology
MH  - Male
MH  - Models, Molecular
MH  - *Mutation, Missense
MH  - NAV1.5 Voltage-Gated Sodium Channel
MH  - Pedigree
MH  - Protein Structure, Secondary
MH  - *Sequence Deletion
MH  - Sodium Channels/chemistry/*genetics
EDAT- 1999/10/06 00:00
MHDA- 1999/10/06 00:01
CRDT- 1999/10/06 00:00
PHST- 1999/10/06 00:00 [pubmed]
PHST- 1999/10/06 00:01 [medline]
PHST- 1999/10/06 00:00 [entrez]
AID - 10.1002/(SICI)1096-8628(19991029)86:5<470::AID-AJMG13>3.0.CO;2-Y [pii]
AID - 10.1002/(sici)1096-8628(19991029)86:5<470::aid-ajmg13>3.0.co;2-y [doi]
PST - ppublish
SO  - Am J Med Genet. 1999 Oct 29;86(5):470-6. doi:
      10.1002/(sici)1096-8628(19991029)86:5<470::aid-ajmg13>3.0.co;2-y.