X-LINKED Clinical Trial
Official title:
DDX3X Related Disorder : Clinical Phenotype, Neuropsychological Profile and Epigenetic Signature.
DDX3X related disorder 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, second, to study the epigenetic signature in a cohort of
individuals with DDX3X 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 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 2018 and 2020, the investigators have already recruited data from individuals with
DDX3X pathogenic variants from several European and Asian genetic centres
The investigators aim to better understand and delineate the genetic syndrome DDX3X.
This genetic disorder was described in 2015 by Lot Snijders Blok et al. (DOI
https://doi.org/10.1016/j.ajhg.2015.07.004:).
Since this first publication of 38 female individuals carrying a pathogenic mutation DDX3X,
15 more individuals have been reported.
The investigators are seeking to better define the phenotype of individuals with pathogenic
variants of DDX3X, 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.
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 DDX3X individuals, this will determine a
disease-specific epigenetic signature. The investigators will then be able to propose an
epigenetic signature for individuals with uncharacterized DDX3X 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 DDX3X 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 DDX3X gene is pathological or not
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