Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04541927 |
| Other study ID # |
RECHMPL20_0472 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
November 1, 2019 |
| Est. completion date |
December 1, 2020 |
Study information
| Verified date |
December 2020 |
| Source |
University Hospital, Montpellier |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
BCL11B related disorder, also known as Gabriele-de-Vries syndrome, is mainly characterised by
developmental delay (DD) and intellectual disability (ID), ranging from mild to severe, and
neuroimaging abnormalities.
The aims of this study are first to better delineate the clinical phenotype, as well as the
neuropsychological profile, and the brain MRI characteristics; and, second, to study the
epigenetic signatures in a cohort of individuals with BCL11B intragenic pathogenic variants.
This work will conduct to a MD thesis of a clinical resident geneticist in France.
Physician that will participate will fill an Excel sheet regarding the clinical and
neuropsychological assessment. The investigators will be also happy to have either CD-ROM or
a link to have access to the brain MRI data as well as a DNA sample with a minimum 0.5ug of
peripheral blood genomic DNA. The investigators will gather the DNA in Montpellier genetic
lab (Dr Mouna BARAT) and send the batch to the Dr Sadikovic' lab.
Between 2019 and 2020, The investigators have already recruited data from individuals with
BCL11B pathogenic variants from several European and American genetic centres.
Description:
The investigators aim to better understand and delineate the genetic syndrome BCL11B (a.k.a.
Intellectual developmental disorder with dysmorphic facies, speech delay, and T-cell
abnormalities syndrome or IDDSFTA).
This genetic disorder was described in June 2017 in the American Journal of Human Genetics
(PMID 28575647).
Since this first publication of 23 individuals carrying the pathogenic mutation BCL11B,
another individual has been reported in the literature (PMID 30549423).
In addition, the first paper focused on the clinical description as well as the effect of
pathogenic BCL11B variations in chromatin regulation.
The investigators are seeking to better define the phenotype of individuals with pathogenic
variants of BCL11B, to better understand intellectual functioning as well as the strengths
and weaknesses of intellectual functioning by collecting standardized neuropsychological
assessments already performed such as WPPSI/WISC and WAIS. For this purpose, The
investigators will gather clinical and neuropsychological data already carried out in the
context of care.
The investigators also aim to gather the cerebral MRI scans already performed in order to
better delimit the cerebral anomalies observed in individuals and if the sequence is adapted,
The investigators will perform VBM studies.
Finally, The investigators will attempt to identify an epigenetic signature in this genetic
disease. To this end, The investigators will collect genomic DNA from peripheral blood
already collected for genetic analysis and send an anonymized batch of samples to our
collaborator, Dr. Bekim Sadicovik. Dr. Bekim Sadicovik and his team will compare the
epigenetic DNA methylation-type markers with the corresponding sex and age controls. If
specific probes are abnormally methylated in BCL11B individuals, this will determine a
disease-specific epigenetic signature. The investigators will then be able to propose an
epigenetic signature for individuals with uncharacterized BCL11B variations (class 3, VUS).
This method will make it possible to define whether the variation is responsible for the
disease or not without going through functional analysis steps that are difficult to
implement routinely.
The expected benefits are a better understanding of BCL11B disease, keys to
neuropsychological rehabilitation, a better understanding of human brain functions, the
possibility of proposing an epigenetic signature for people in whom it is not possible to
decide whether a variation in the BCL11B gene is pathological or not
