Finding the cause of the phenotype that resembles Marfan syndrome in a single family.
ID
Source
Brief title
Condition
- Connective tissue disorders (excl congenital)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Pathogenic variant in a gene that explains the phenotype in the family
Secondary outcome
Understanding the pathogenesis of the connective tissue disorder in the family
Background summary
Marfan syndrome is a well-known disorder characterized by widely spread signs
and symptoms, of which the most important ones are dislocation of the lens,
skeletal deformities including pectus carinatum formation, scoliosis and
arachnodactyly, and decreased elasticity and firmness of the aorta and other
large blood vessels which may lead to dissection. A multi-fold of additional
signs and symptoms occurs, such as dural ectasias and striae. Marfan syndrome
is caused by variants in the gene Fibrillin type I.
For years a family is known in the AMC with a connective tissue disorder that
resembles Marfan syndrome to a very great extent. The affected family members
fulfil the clinical criteria for the diagnosis Marfan syndrome. However, no
variant could be found in Fibrillin type I or in one of the other genes of
which it is known that variants may cause a phenotype resembling Marfan
syndrome.
Study objective
Finding the cause of the phenotype that resembles Marfan syndrome in a single
family.
Study design
Exome sequencing in 3 affected family members and 1 unaffected family member,
checking for variants in genes present in affected members and not in the
unaffected member. If the numberof candidate genes remain too high exome
sequencing will be performed in two additional unaffected family members. We
expect to find a small number of candidate genes,. Due to the extensive
knowledge of proteins involved in establishing a normally functioning
connective tissue we expect to be able to indicat which candidate gene is most
likelt the cause in this family. Subsequently, further functional studies will
be performed.
Study burden and risks
Of all affected and non-affected family members DNA is stored at the time they
have been investigated because of the familial connective tissue disorder.
Therefore no further sampling is needed and the burden of the study is nil. If
functional studies will be needed these will likely be performed in an animal
model. However, if case these will be needed in one of the affected family
members it will be performed in the affected adult male.
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
Patients:
Marfan-like syndrome
willing to participate
Control
Not affected by Marfan-like syndrome as it runs in the family
willing to participate
Exclusion criteria
none
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 | NL65695.018.18 |