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Improvement of DIAgnostic and Phenotype-genotype Correlation Studies in Patients With MYOpathy Suspected of TITinopathy

NCT03998540 · Status: RECRUITING · Type: OBSERVATIONAL · Enrollment: 50

Last updated 2024-02-28

No results posted yet for this study

Summary

Due to the widespread use of NGS, TTN is emerging as a major causative gene in neuromuscular disorders, with high clinical heterogeneity. The mechanisms underlying the phenotypic variability and mode of inheritance (recessive or dominant) of titinopathies are poorly understood. They involve the primordial structural functions of titin on the formation and stability of the sarcomere, as well as its interactions with other proteins. We identified by NGS, in patients with skeletal myopathy (with or without cardiomyopathy), several potentially disease causing TTN variants. The specific aims of the present project are to implement functional studies (transcripts, protein analyses, in vitro protein-protein interaction studies) to evaluate the effect of TTN variants on the transcripts and protein in order to perform phenotype-genotype correlation studies. We participate to the national "titin network" and to international efforts for the understanding of the molecular bases of titinopathies. Genomic characterisation opens the way to develop cellular models of titinopathy, derived from patient biopsies. This is also a mandatory first step for the design of novel therapeutic approaches.

Conditions

Interventions

DIAGNOSTIC_TEST

Western blot

Western-blot analysis of a giant protein, with specific antibodies directed against C-ter and N-Ter of the protein

OTHER

Protein interaction studies

Analyses of several interacting proteins by specific Western-blot and in-vitro tests.

OTHER

Mass Spectometry

samples previously used for western blotting will be subjected to mass spectrometry analysis

OTHER

RNA seq

analyze muscle gene expression in patients with titinopathies in our cohort by RNAseq

Sponsors & Collaborators

  • University Hospital, Montpellier

    lead OTHER

Eligibility

Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2019-12-05
Primary Completion
2024-12-05
Completion
2025-05-05

Countries

  • France

Study Locations

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Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT03998540 on ClinicalTrials.gov