The objective of the study is to show that it is in principle possible to diagnose carriership of both partners of a couple by means of exome sequencing (proof of principle)
ID
Source
Brief title
Condition
- Chromosomal abnormalities, gene alterations and gene variants
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary study parameter will be the diagnosis, by the 'blinded' laboratory,
of carriership of both parents for the disorder of thier child.
Secondary outcome
Potentially we will find carriership of another recessive disorder, but the
chance to do so is low
Background summary
Children of conanguineoud parents are, in comparison to children of
non-consanguineous parents, at increased risk to have an autosomal recessive
condition. This occurs only when both parents are carriers of a mutation in the
concerning responsible gene. When both parents are carriers of a mutation is
such a gene, each of their children will have 25% chance to develop the
concerning disorder; in case they are both carriers of mutations in 2 such
genes the risk becomes 44%, and so on. The probability that both parent are
carriers is, however, much lower than the chance that they are not both
carriers. For first cousin marriages the probability that both partners are
carriers is less than 8%. It would be a great relief for consanguineous parents
to learn that they are not both carriers, while at the same time finding
carriership in both partners of the other couples would increase their
possibilities for an informed reproductive choice substantially.
Study objective
The objective of the study is to show that it is in principle possible to
diagnose carriership of both partners of a couple by means of exome sequencing
(proof of principle)
Study design
Blood samples of both parents of children with an autosomal recessive
condition, which is already characterized at DNA level, will be presented for
exome sequencing, without information about the disorder in the child, to a
laboratory that was not involved already in the diagnosis in this family. Exome
sequancing therefore is performed blindly. If te laboratory succeeds in
diagnosing carriership for the concerning disorder in the child, the method can
be tried out in future in a prospective study of consanguineous parents who
have not (yet) an affected child.
Study burden and risks
Parents are invited to come to the hospital or visited at home. We wil take
just one blood sample of each parent. There is a very very small chance of un
unsollicited finding.
De Boelelaan 1117
Amsterdam 1081 HV
NL
De Boelelaan 1117
Amsterdam 1081 HV
NL
Listed location countries
Age
Inclusion criteria
Consanguineous and non-consanguineous couples who have or had a child with an autosomal recessive disorder, whose DNA's (of couple and child) have not been tested before in the laboratory involved in the exome sequencing (in order to guarantee that the testing is performed blindly)
Exclusion criteria
When information on the responsible mutations in the child is lacking
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 | NL39242.029.12 |