To gain insight into the biological pathways that are influenced by the CEEx30/31 mutations.
ID
Source
Brief title
Condition
- Chromosomal abnormalities, gene alterations and gene variants
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
We will compare the effects of the variants in CEEx30/31 with those of RSTS
patients (CREBBP loss-of-function), patients with a duplication of CREBBP
(CREBBP gain-of-function), and healthy controls on i) gene expression by
RNA-Seq, ii) activity of DNA segments by ATAC-Seq, and iii) protein
interactions with DNA using ChIP-seq.
Secondary outcome
n.a.
Background summary
We recently evaluated twenty-four patients with intellectual disability who had
a mutation in CREBBP or EP300. Although mutations in these genes usually cause
Rubinstein-Taybi syndrome (RSTS), the typical signs of RSTS, consisting of
specific facial features, broad thumbs and broad big toes were absent, implying
that the patients had different, previously unknown syndromes. All patients had
a mutation in exon 30 or 31 of CREBBP/EP300 (*CEEx30/31*), a region in which,
thus far, no mutations had been found in patients with RSTS.
Interestingly, the facial characteristics of patients with mutations at the 3*
end of the CEEx30/31 region resembled those of patients with a duplication of
CREBBP. Therefore, the mutations may result in a gain-of-function, in contrast
to the loss-of-function that causes RSTS. The characteristics of patients with
mutations at the 5* end of the CEEx30/31 region did not resemble one-another
markedly. We therefore hypothesize that these mutations perturb other of the
numerous functions of CREBBP/EP300 (both important cofactors of transcription).
Study objective
To gain insight into the biological pathways that are influenced by the
CEEx30/31 mutations.
Study design
Observational study with invasive measurements
Study burden and risks
The risk and burden associated with a single skin biopsy are negligible,
especially when taken during surgery using the surgical incision that already
needs to be made for clinical care reasons.
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
1. Individuals with either a) a mutation in CEEx30/31, b) RSTS, c) a dup 16p13.3, d) a dup 22q13.2, and e) healthy age-, and sex-matched controls.
2. availability of stored fibroblasts or a planned surgical intervention for patient care reasons
3. Patients and/or parent(s)/caregiver(s)/legal representatives able to provide written permission
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 | NL65113.018.18 |