Better Delineation of YY1 Related Phenotype and Epigenetic Signatures.

Description

The investigators aim to better understand and delineate the genetic syndrome YY1 (a.k.a. Gabriele-de-Vries syndrome).

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 YY1, 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 YY1 variations in chromatin regulation.

The investigators are seeking to better define the phenotype of individuals with pathogenic variants of YY1, 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 YY1 individuals, this will determine a disease-specific epigenetic signature. The investigators will then be able to propose an epigenetic signature for individuals with uncharacterized YY1 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 YY1 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 YY1 gene is pathological or not

Details