Genotype/Phenotype Correlation of MORC2 Mutations
PhenoMORC2
Deciphering MORC2 Genotype/Phenotype Correlation to Improve Patient Diagnostic
2 other identifiers
observational
45
1 country
12
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for all trials
Started Sep 2025
12 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 27, 2025
CompletedFirst Posted
Study publicly available on registry
June 26, 2025
CompletedStudy Start
First participant enrolled
September 1, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
September 1, 2027
July 4, 2025
July 1, 2025
1 year
May 27, 2025
July 3, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Epigenetic biomarker levels
Quantification of epigenetic biomarkers in patient and control-derived cells (number of reads in patients vs controls)
At inclusion
Secondary Outcomes (5)
RNA-seq
At inclusion
Detection and quantification of specific nucleic acid biomarkers in patient's serum
At inclusion
Quantification of nucleic acid biomarkers in patient's cerebrospinal fluid
At inclusion
Quantification of proteic biomarkers in patient's serum
At inclusion
Quantification of proteic biomarkers in patient's cerebrospinal fluid (CSF)
At inclusion
Study Arms (3)
Charcot-Marie-Tooth patients : Patients presenting with length-dependent sensitive-motor axonal neur
Patients presenting with length-dependent sensitive-motor axonal neuropathy
DIFGAN patients
Patients presenting with DIFGAN syndrome : developmental delay, impaired growth, dysmorphic facies and axonal neuropathy
Control
Control group without any neurological disorder
Interventions
under the arm using a 3 mm punch, with local anaesthesia, in the investigating centres.
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.
Eligibility Criteria
This study will focus on children and adults suffering from a MORC2 gene mutation, and presenting a CMT or DIFGAN phenotype.
You may qualify if:
- Presence of a mutation in the MORC2 gene, identified during an evaluation for peripheral neuropathy or intellectual disability
- 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
You may not qualify if:
- 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
- Individuals not affiliated with a social security system or not benefiting from an equivalent health coverage scheme
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (12)
CHU de Besançon
Besançon, 25030, France
CHRU Brest
Brest, 29200, France
CHU Grenoble
Grenoble, 38700, France
CH de Versailles
Le Chesnay, 78150, France
Service de Génétique moléculaire, pharmacogénétique, hormologie Hôpital Bicêtre
Le Kremlin-Bicêtre, 94270, France
Hospices Civils de Lyon
Lyon, 69317, France
CHU Marseille
Marseille, 13005, France
CHU de Nantes
Nantes, 44000, France
CH Pitié Salpêtrière
Paris, 75013, France
Hôpital Necker
Paris, 75015, France
CHU de Saint-Etienne
Saint-Etienne, 42270, France
CHU Strasbourg
Strasbourg, 67000, France
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- OTHER
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 27, 2025
First Posted
June 26, 2025
Study Start
September 1, 2025
Primary Completion (Estimated)
September 1, 2026
Study Completion (Estimated)
September 1, 2027
Last Updated
July 4, 2025
Record last verified: 2025-07
Data Sharing
- IPD Sharing
- Will not share