Study of New Mutations in Cone Disorders

Recruiting

• Conditions: Cone Rod Dystrophy; Retinal Dystrophy, Cone-Rod; Macular Degeneration; Cone Dystrophy
• Interventions: Genetic: Blood and/or skin biopsy

• Registration Number: NCT04658251
• Lead Sponsor: University Hospital, Lille

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-12-01
• Study First Submitted QC: 2020-12-07
• Study First Posted: 2020-12-08
• Study Start: 2021-03-03
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-16
• Last Update Posted: 2022-05-17
• Primary Completion: 2026-03
• Study Completion: 2026-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Patients with an intronic variant unknown in a gene implicated in cone disorders.	Blood and/or skin biopsy	-

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

CHU lille; 🇫🇷 Lille, France