Modifying Factors in Striated Muscle Laminopathies
Key facts
- Who runs it
- Institut National de la Santé Et de la Recherche Médicale, France
- Where
- France8 sites in 1 countryChoose a country to see its sites
- Trial code
- Status
- Recruiting
- People taking part
- 40 people, planned
- Started
- 8 Sept 2022
- Expected to end
- 30 Dec 2027
- Type of study
- Interventional
- Treatments tested
- Skin Biopsy
- Muscle biopsy
- Record updated
- 4 March 2026
Who can take part
- Age
- 2 years and older
- Sex
- Women and men
- Healthy volunteers
- Cannot take part
The registry criteria, word for word
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Who can take part
- Patient with an LMNA mutation that has led to the diagnosis of laminopathy affecting striated muscle
- Presenting the symptoms of the disease, whether they are index cases or related to this index case (muscle weakness, tendon retractions with or without respiratory or cardiac involvement)
- Have no contraindication to muscle or skin biopsy, i.e., 1) presence of a history of allergy to latex, antiseptics, local anesthetics and adhesive dressings, 2) Current oral or parenteral anticoagulant therapy (anti-vitamin K, heparins, anti-platelet agents, anti-factor X, anti-thrombin), 3) History of inherited (haemophilias, platelet diseases) or acquired (vitamin K deficiency, liver failure) coagulation disorders
- Patients (adult participant) or both holders of parental authority (minor participant) must sign a free and informed consent. If a minor has only 1 legal representative, the latter must attest to this on the consent form
- Patients affiliated to the general French social security system, to the French Universal Medical Coverage (CMU) or to any French equivalent scheme
Who cannot take part
- Pregnant or breastfeeding women
- Adult subject to legal protection measures (safeguard of justice, curatorship and guardianship)
This trial has no sites in United States.
It has sites in one country. Choose a country to see its sites.
About the trial
What the trial wants to find out
Mutations in the LMNA gene, which codes for lamins A and C, proteins of the nuclear lamina, are responsible for a wide spectrum of pathologies, including a group specifically affecting striated skeletal and cardiac muscles, with cardiac involvement being life-threatening. At the skeletal muscle level, a wide phenotypic spectrum has been described, ranging from severe forms of congenital muscular dystrophy to less severe forms of limb-girdle muscular dystrophy. The great clinical variability of striated muscle laminopathies, both inter- and intra-familial, can be observed in the age of onset, severity of signs and progression of muscle and heart involvement. To date, more than 400 LMNA mutations have been associated with striated muscle laminopathies (www.umd.be/LMNA/), highlighting strong clinical and genetic heterogeneity. A few recurrent mutations linked to a difference in severity have been identified. However, these genotype-phenotype relationships and the rare cases of digenism reported do not explain all the clinical variability of laminopathies. Therefore, there are probably other factors of severity than the causative mutation, called "modifier genes".
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Identification of such modifier genes has been initiated by studying a large family with significant clinical variability in the age of onset of muscle signs. A segregation analysis within this family identified 2 potential modifier loci. High-throughput sequencing restricted to these 2 regions according to phenotypic subgroups did not led to meaningful results so far. In addition, an international retrospective study of the natural history of early muscle laminopathies has allowed the investigators to highlight a strong inter-family clinical variability in patients carrying recurrent mutations. The investigators thus have strong preliminary data that could allow them to identify modifying genetic factors in a cohort of patients carrying a mutation in the LMNA gene.
In order to identify these factors that modulate the clinical severity of laminopathies, the investigators wish to collect biological material (muscle and/or skin biopsies) from patients carrying a mutation in the LMNA gene. The study of this biological material using multi OMICs technics will allow the investigators to identify and functionally validate the action of these modifying genes.
OMIICs is a set of techniques for characterising biological molecules using high-throughput approaches such as DNA sequencing, RNA sequencing and/or chromatin conformation (ATACseq...), proteins.
The group in the trial
- Collection of biological materialOther group
Patients carrying LMNA mutation with no contrindication for skin and/or muscle biopsy: * from large families with striking intrafamilial phenotypic variability (3 families identified). * patients carrying p.Arg453Trp or p.Glu358Lys LMNA gene mutations
Treatment: Skin Biopsy and Muscle biopsy
Questions to ask the study team
- How often do I need to come in, and for how long each time?
- Are travel costs paid?
- Can I keep my own doctor?
- What happens if I want to stop?
Contact the study team: see the registry record → Contacts and Locations
Print a page for my doctorData and sources
- Registry record
- Listed on ClinicalTrials.gov.
- Official title
- Identification of Genetic Modifying Factors in Striated Muscle Laminopathies
- Record updated
- 4 March 2026