Linked Life Data

10590249

Source:http://linkedlifedata.com/resource/pubmed/id/10590249

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2000-1-4
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0009-7330
pubmed:author
pubmed:issnType
Print
pubmed:volume
85
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1206-13
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:articleTitle
A single Na(+) channel mutation causing both long-QT and Brugada syndromes.
pubmed:affiliation
Departments of Clinical Genetics , Academic Medical Center, Amsterdam, The Netherlands.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't