BCL11B Related Disorder : Clinical Phenotype, Neuropsychological Profile, Brain MRI Characteristics and Epigenetic Signatures.
BCL11B Related Disorder : Clinical Phenotype, Neuropsychological Profile, Brain MRI Characteristics and Epigenetic Signatures.
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.
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
Inclusion criteria:
- BCL11B intragenic pathogenic SNV (Single Nucleotide Variant)
Exclusion criteria: