The objective of this research is to develop a method which can identify among all consanguineous couples the ones which are at high risk.
ID
Source
Brief title
Condition
- Congenital and hereditary disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
For every individual a genotype is formed by using the SNP's. With this
information for all couples the inbreeding coefficient is estimated. The
estimates of inbreeding coefficient will be used as an outcome variable in the
case-controle study. The expected outcome of these analyses is that the actual
degree of relatedness (i.e. estimated from genotype data) of the cases is
highger than the degree of relatedness of the controls.
For our cohort design a logistic regression analysis will be performed with the
inbreeding coefficient as independent variable. With this information an
odds-ratio can be estimated for the relationship between the inbreeding
coefficient and the risk of having a child with an autosomal recessive
disorder.
Secondary outcome
not applicable
Background summary
It is a known fact that children of consanguineous parents have a higher risk
of being affected by an autosomal recessive disorder. For children of first
cousin couples, this risk is only a few percent higher than the risk for
couples that are not related. This means that some couples have a significant
high risk, while the majority has no or a very limited excess risk. At this
point it is not possible to dfiferentiate between couples that have a high
risk, and those who have a limited or no excess risk.
Study objective
The objective of this research is to develop a method which can identify among
all consanguineous couples the ones which are at high risk.
Study design
The risk of autosomal recessive diseare in the offspring of consanguineous
couples is conditonal on the presence of identical alleles with pathological
mutations in both parents, decending from the common ancestor. The more DNA
identical by descent is shared by the parents, the higher the risk.
By means of SNP analysis the proportion of DNA shared by consanguineous parents
can be estimated. This would allow us to estimate better risk figures for
consanguineous parents with a desire to have children.
We will use two different approaches in this study:
The case-control design will allow us to test whether consanguineous partners
with children affected by autosomal recessive diseases share more DNA,
identical by descent, than consanguineous partner who are believed to be
related to the same degree, but only have healthy children. For our cohort
design we will contact consanguineous couples with a desire to have children.
The cohort design will be used to obtain different risk figure estimates for
the different proportions of DNA shared in consanguineous couples.
Study burden and risks
Given the nature of this research - obtaining an extensive family history and a
saliva sample - we don't expect the participants to be at risk. However, the
only possible risk that may occur is in a situation where the privacy is at
risk. We will try to minimize this by the arrangement as mentioned in this
form.
Postbus 7057
1007 MB Amsterdam
NL
Postbus 7057
1007 MB Amsterdam
NL
Listed location countries
Age
Inclusion criteria
Cases :
-are defined as consanguineous parents of a child that is affected by an autosomal recessive disorder
-This autosomal recessive disorder has not occurred in the family before.
Controls :
-are defined as consanguineous parents without (previous) affected children and with at least three healthy children.
In our study we restrict ourselves to couples with an inbreeding coefficient (F) of at least F= 1/128. This inbreeding coefficient must be clear from the family tree that include ALL third-degree family members (including great grandparents) of the couple, to make sure equally reliable and sufficient information is obtained in all pedigrees. ;Cohort:
Consanguineous couples with a desire to have children. There are no previous cases of autosomal recessive disorders in the family.
Exclusion criteria
- the nature of the disorder of the affected child is not clear
- the disease has occurred in the family before
- the inbreeding coefficient is less than 1/128
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 | NL24748.029.08 |