Study of New Mutations in Cone Disorders

NCT04658251 | Recruiting

• 2 other identifiers: 2020_662020-A02559-30
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

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

Conditions

Retinal Dystrophy, Cone-Rod; Cone Dystrophy; Cone Rod Dystrophy; Macular Degeneration

Keywords

intronic variant; splicing; functional test; cone disorders; retinal dystrophy; RNA; minigene splice assay; cells

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• 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 patient RNA transcripts

  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 lymphoblastoid lines

  at 2 years

• Effect of the intronic variant on RNA by analysis of transcripts from IPSCs (induced pluripotent stem cells)

  at 2 years

Study Arms (1)

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

Genetic: Blood and/or skin biopsy

Interventions

Blood and/or skin biopsy GENETIC

Blood and/or skin biopsy will be withdrawn, for RNA extraction in order to test the effect of the variant on splicing.

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

Eligibility Criteria

• Age: 3 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients carrying an intronic variant of unknown significance (or carrying an exonic variant with a predicted effect on splicing) in a gene implicated (or potentially implicated) in cone disorders, will be included in the study.

You may qualify if:

• clinical diagnosis of cone disorder
• identification of a variant of unknown significance
• possibility of samplings
• informed consent

You may not qualify if:

• no variant of unknown significance identified
• no informed consent

Sponsors & Collaborators

• University Hospital, Lille: lead

Study Sites (1)

CHU lille

Lille, 59037, France

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples: * Paxgen tubes (2 x 5ml) and heparin tubes (2 x 7ml) will be collected (maximum 32 ml) for RNA extraction if the candidate gene is expressed in the leucocytes * Potentially 2 Vacutainer CPT tubes for IPSC generation Biopsy: Potentially a skin biopsy (3 mm diameter) will be carried out if the gene is not expressed in leucocytes

MeSH Terms

Conditions

Cone-Rod Dystrophies; Cone Dystrophy; Macular Degeneration; Retinal Dystrophies

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Retinal Degeneration; Retinal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Claire-Marie DHAENENS, MD

  University Hospital, Lille

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Claire-Marie DHAENENS, MD

CONTACT

0320445962; claire-marie.dhaenens@chru-lille.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2020
• First Posted: December 8, 2020
• Study Start: March 3, 2021
• Primary Completion: March 1, 2026
• Study Completion: March 1, 2026
• Last Updated: May 17, 2022

Record last verified: 2022-05

Locations

FR (1)