Charcot Marie Tooth Disease, Developmental Delay (Disorder), DIFGAN, Dysmorphic Facies and Axonal Neuropathy, Impaired Growth
Conditions
Keywords
Charcot-Marie-Tooth, DIFGAN, Human silencing hub complex, genotype-phenotype correlation, MORC2, DNA dalage repair, transcriptional modulation, EPIGENETIC
Brief summary
The Microrchidia CW-type zinc finger 2 (MORC2) gene encodes a protein expressed in all tissues and enriched in the brain. It is involved in Charcot-Marie-Tooth disease, with mire than 30 families presenting MORC2 mutations. Recently, MORC2 mutation have been shown to be responsible for more complex phenotypes like DIFGAN: developmental delay, impaired growth, dysmorphic facies and axonal neuropathy. Different mutations are responsible from a diverse spectrum of phenotype, from CMT to DIFGAN. MORC2 is involved, through its ATPase activity, in DNA repair, chromatin remodeling and epigenetic silencing via the Human silencing hub (HUSH) complex. Our hypothesis is that the hypo- or hyper-activation of the HUSH complex by different MORC2 mutations could be responsible for different phenotypes in patients. The aim of this study is to perform a genotype-phenotype correlation study in patients presenting MORC2 mutations.
Interventions
DIAGNOSTIC_TESTSkin biopsy
under the arm using a 3 mm punch, with local anaesthesia, in the investigating centres.
DIAGNOSTIC_TESTBlood sample
3 classical 4ml tubes samples per patients, using the routine blood sampling technique, in the investigating centres. For children, blood sampling volume will be adapted to the patient's weight according to L.1121-1 of the French public health code.
Sponsors
Hospices Civils de Lyon
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
4 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Presence of a mutation in the MORC2 gene, identified during an evaluation for peripheral neuropathy or intellectual disability * Patient has undergone electromyography (EMG) or is able to undergo EMG during the inclusion visit * Affiliation with the national health insurance system * Informed consent from the patient if an adult, or from parents/legal guardians if the patient is a minor
Exclusion criteria
* Presence of another mutation responsible for peripheral neuropathy or intellectual disability * Refusal to undergo biological sample collection * Regulatory
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Epigenetic biomarker levels | At inclusion | Quantification of epigenetic biomarkers in patient and control-derived cells (number of reads in patients vs controls) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| RNA-seq | At inclusion | quantification of specific mRNA sequences in patient-derived cells (RNA copy number in patient vs control) |
| Detection and quantification of specific nucleic acid biomarkers in patient's serum | At inclusion | Quantification of nucleic acid biomarkers in the patient's serum (number of reads in patients vs control) |
| Quantification of nucleic acid biomarkers in patient's cerebrospinal fluid | At inclusion | Quantification of nucleic acid biomarkers in the patient's cerebrospinal fluid (CSF) (number of reads in patients vs control) |
| Quantification of proteic biomarkers in patient's serum | At inclusion | Quantification of proteic biomarkers in the patient's serum (µg/mL) |
| Quantification of proteic biomarkers in patient's cerebrospinal fluid (CSF) | At inclusion | Quantification of proteic biomarkers in the patient's cerebrospinal fluid (CSF)(µg/mL) |
Countries
France
Contacts
CONTACTShams RIBAULT, MD
Outcome results
None listed