Better Delineation of CDK13 Related Phenotype and Epigenetic Signature.
Better Delineation of CDK13 Related Phenotype and Epigenetic Signature.
CDK13 related disorder is mainly characterised by developmental delay (DD) and intellectual
 disability (ID), ranging from mild to severe, and malformation syndrome.

 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 CDK13 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
 CDK13 pathogenic variants from France and several European genetic centres.
The investigators aim to better understand and delineate the genetic syndrome CDK13 This
 genetic disorder was described in Sepember 2016 in Nature Genetics (PMID 27479907).

 Since this first publication of 6 individuals carrying the pathogenic mutation CDK13, 37
 other individuals carrying a pathogenic mutation of CDK13 have been reported in the
 litterature The investigators are seeking to better define the phenotype of individuals with
 pathogenic variants of CDK13, 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 CDK13 individuals, this will determine a
 disease-specific epigenetic signature. The investigators will then be able to propose an
 epigenetic signature for individuals with uncharacterized CDK13 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 CDK13 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 CDK13 gene is pathological or not
Inclusion criteria:

 - CDK13 intragenic pathogenic SNV (Single Nucleotide Variant)

 Exclusion criteria:

 -  no pathogenic SNV in CDK13

 -  no consent for the study