Ignite Creation Date:
2024-05-06 @ 2:39 PM
Last Modification Date:
2024-10-26 @ 1:34 PM
Study NCT ID:
NCT04381715
Status:
UNKNOWN
Last Update Posted:
2020-05-14
First Post:
2020-05-06
Brief Title:
Better Delineation of YY1 Related Phenotype and Epigenetic Signatures
Sponsor:
University Hospital Montpellier
Organization:
University Hospital Montpellier
Study Overview
Official Title:
YY1 Related Disorder Clinical Phenotype Neuropsychological Profile Brain MRI Characteristics and Epigenetic Signatures
Status:
UNKNOWN
Status Verified Date:
2020-05
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
YY1 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 YY1 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 05ug 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 YY1 pathogenic variants from several European and American genetic centres
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 YY1 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 05ug 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 YY1 pathogenic variants from several European and American genetic centres
Detailed Description:
The investigators aim to better understand and delineate the genetic syndrome YY1 aka 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 WPPSIWISC 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
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 WPPSIWISC 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None