Genotype/Phenotype Correlation of MORC2 Mutations

Recruiting

• Conditions: Charcot Marie Tooth Disease; DIFGAN; Developmental Delay (Disorder); Impaired Growth; Dysmorphic Facies and Axonal Neuropathy

• Registration Number: NCT07038239
• Lead Sponsor: Hospices Civils de Lyon

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-05-27
• Study First Submitted QC: 2025-06-17
• Study First Posted: 2025-06-26
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-03
• Last Update Posted: 2025-07-04
• Study Start: 2025-09-01
• Primary Completion: 2026-09
• Study Completion: 2027-09-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 45

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 exclusion criteria:
• 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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Epigenetic biomarker levels	At inclusion	Quantification of epigenetic biomarkers in patient and control-derived cells (number of reads in patients vs controls)

Secondary Outcome Measures

Name	Time	Method
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)
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)

Trial Locations

Locations (12)

CHU de Besançon; 🇫🇷 Besançon, France

CHRU Brest; 🇫🇷 Brest, France

CHU Grenoble; 🇫🇷 Grenoble, France

CH de Versailles; 🇫🇷 Le Chesnay, France

Service de Génétique moléculaire, pharmacogénétique, hormologie Hôpital Bicêtre; 🇫🇷 Le Kremlin-Bicêtre, France

Hospices Civils de Lyon; 🇫🇷 Lyon, France

CHU Marseille; 🇫🇷 Marseille, France

CHU de Nantes; 🇫🇷 Nantes, France

CH Pitié Salpêtrière; 🇫🇷 Paris, France

Hôpital Necker; 🇫🇷 Paris, France

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