Study of New Mutations in Cone Disorders

Macular Degeneration Clinical Trial

— INTROCONE  

Official title:

Functional Study of Intronic Variants in Inherited Cone Disorders

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04658251
• Other study ID #: 2020_66
• Secondary ID: 2020-A02559-30
• Status: Recruiting
• Start date: March 3, 2021
• Est. completion date: March 2026

Study information

• Verified date: May 2022
• Source: University Hospital, Lille
• Contact: Claire-Marie DHAENENS, MD
• Phone: 0320445962
• Email: claire-marie.dhaenens[@]chru-lille.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: March 2026
• Est. primary completion date: March 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cone Dystrophy
• Cone Rod Dystrophy
• Macular Degeneration
• Retinal Dystrophies
• Retinal Dystrophy, Cone-Rod

Intervention

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Blood and/or skin biopsy will be withdrawn, for RNA extraction in order to test the effect of the variant on splicing.

Locations

Country	Name	City	State
France	CHU lille	Lille

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Lille

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effect of the intronic variant on RNA splicing observed in cellulo and/or on patient cells,	Analysis of RNA transcripts of the gene carrying a variant of unknown significance.	at 2 years
Secondary	Effect of the intronic variant on RNA by Minigene splice assay in transient cell cultures		at 2 years
Secondary	Effect of the intronic variant on RNA by analysis of patient RNA transcripts		at 2 years
Secondary	Effect of the intronic variant on RNA by analysis of transcripts from fibroblasts		at 2 years
Secondary	Effect of the intronic variant on RNA by analysis of transcripts from lymphoblastoid lines		at 2 years
Secondary	Effect of the intronic variant on RNA by analysis of transcripts from IPSCs (induced pluripotent stem cells)		at 2 years