Study of New Mutations in Cone Disorders

Overview

High throughput sequencing gives the opportunity to improve the genetic diagnosis for patients suffering from retinal dystrophies and specially from cone disorders. However, a large number of mutations are identified, mostly in introns of the genes, and in silico analysis are not sufficient to assign the pathogenicity of these mutations, without which the diagnosis confirmation cannot be done. For that purpose, a functional analysis of intronic variants of unknown significance detected in patients, with minigene splice assays in parallel with the analysis of the effect of the variant on splicing directly in the cells of the patient, by analyzing the RNA from leucocytes, fibroblasts, lymphoblastoïd cells or precursor of photoreceptor cells, which is the only proof of pathogenicity for variants

Full Title of Study: “Functional Study of Intronic Variants in Inherited Cone Disorders”

Study Type

  • Study Type: Observational
  • Study Design
    • Time Perspective: Prospective
  • Study Primary Completion Date: February 2024

Interventions

  • Genetic: Blood and/or skin biopsy
    • Blood and/or skin biopsy will be withdrawn, for RNA extraction in order to test the effect of the variant on splicing.

Arms, Groups and Cohorts

  • Patients with an intronic variant unknown in a gene implicated in cone disorders.

Clinical Trial Outcome Measures

Primary Measures

  • Effect of the intronic variant on RNA splicing observed in cellulo and/or on patient cells,
    • Time Frame: at 2 years
    • Analysis of RNA transcripts of the gene carrying a variant of unknown significance.

Secondary Measures

  • Effect of the intronic variant on RNA by Minigene splice assay in transient cell cultures
    • Time Frame: at 2 years
  • Effect of the intronic variant on RNA by analysis of patient RNA transcripts
    • Time Frame: at 2 years
  • Effect of the intronic variant on RNA by analysis of transcripts from fibroblasts
    • Time Frame: at 2 years
  • Effect of the intronic variant on RNA by analysis of transcripts from lymphoblastoid lines
    • Time Frame: at 2 years
  • Effect of the intronic variant on RNA by analysis of transcripts from IPSCs (induced pluripotent stem cells)
    • Time Frame: at 2 years

Participating in This Clinical Trial

Inclusion Criteria

  • clinical diagnosis of cone disorder – identification of a variant of unknown significance – possibility of samplings – informed consent Exclusion Criteria:

  • no variant of unknown significance identified – no informed consent

Gender Eligibility: All

Minimum Age: 3 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • University Hospital, Lille
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Claire-Marie DHAENENS, MD, Principal Investigator, University Hospital, Lille
  • Overall Contact(s)
    • Claire-Marie DHAENENS, MD, 0320445962, claire-marie.dhaenens@chru-lille.fr

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.