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.
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
Presence of another mutation responsible for peripheral neuropathy or intellectual disability
Refusal to undergo biological sample collection
Pregnant, postpartum, or breastfeeding women
Individuals deprived of liberty by judicial or administrative decision
This study will focus on children and adults suffering from a MORC2 gene mutation, and presenting a CMT or DIFGAN phenotype.
Other
Prospective
Skin biopsy
Diagnostic testunder the arm using a 3 mm punch, with local anaesthesia, in the investigating centres.
Blood sample
Diagnostic test3 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.
Epigenetic biomarker levels
Quantification of epigenetic biomarkers in patient and control-derived cells (number of reads in patients vs controls)
RNA-seq
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
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
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
Quantification of proteic biomarkers in the patient's serum (µg/mL)
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