In the present study we aim to identify the genetic modifiers in this family which underlie differences in severity and type of phenotype by means of linkage analysis.
ID
Source
Brief title
Condition
- Cardiac arrhythmias
- Chromosomal abnormalities, gene alterations and gene variants
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The discovery of genetic modifiers which are associated with the cardiac
electrical phenotype and SCD may allow improved risk stratification and
individualised tailoring of preventive and therapeutic treatment not only for
the SCN5A 1795insD family but also for other populations at risk for SCD.
Secondary outcome
Not applicable.
Background summary
A large Dutch family carrying the SCN5A 1795insD mutation which encodes for the
cardiac sodium (Na+) channel is characterised by a high number of nocturnal
sudden cardiac death (SCD) and multiple arrhythmia syndromes. We documented an
extensive variability in the type and severity of symptoms in this family. We
have shown that these symptoms could in part be attributable to the biophysical
properties of a multi-dysfunctional mutant Na+ channel. Here we hypothesize
that genetic background plays a significant role in determining the ultimate
cardiac phenotype. In support of this hypothesis, studies we carried out on
transgenic mice of two different inbred genetic strains both carrying the
murine equivalent of the SCN5A 1795insD mutation, demonstrated that the
phenotype is more severe in one genetic background compared to the other.
Study objective
In the present study we aim to identify the genetic modifiers in this family
which underlie differences in severity and type of phenotype by means of
linkage analysis.
Study design
After obtaining informed consent, the participants will provide; for
genotyping: 27 ml of blood (taken by venapuncture) or saliva (in a 10 ml tube);
for phenotyping: a single baseline ECG and a follow up ECG after at least one
year. The phenotype and genotype of the subjects in this study will be used for
linkage analyses. Comparing genotype and phenotype from mutation carriers and
non-mutation carriers will identify genes that are associated with the cardiac
electrical phenotype and SCD.
Study burden and risks
The burden for the participants is the provision of their time, blood or saliva
and ECG, with a possible risk for a haematoma following venapuncture. Benefit;
with this research we will be more informed on a selection of candidate genes
and have better chance to discover genes which confer risk for SCD, which may
not only ameliorate SCD risk stratification for their children, family and
future offspring, but also for other populations at risk for SCD.
Postbus 22660
1100 DD Amsterdam
NL
Postbus 22660
1100 DD Amsterdam
NL
Listed location countries
Age
Inclusion criteria
Having conceived 1 or more children carrying the SCN5A 1795insD mutation with someone who is also carrying this mutation (i.e. the individual is a spouse and parent of a mutation carrier)
Exclusion criteria
No informed consent
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL16269.018.07 |