Cone Dystrophy, Cone Rod Dystrophy, Macular Degeneration, Retinal Dystrophy, Cone-Rod
Conditions
Keywords
intronic variant, splicing, functional test, cone disorders, retinal dystrophy, RNA, minigene splice assay, cells
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
Interventions
GENETICBlood 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Blood and/or skin biopsy will be withdrawn, for RNA extraction in order to test the effect of the variant on splicing.
Sponsors
University Hospital, Lille
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
3 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 |
Countries
France
Contacts
PRINCIPAL_INVESTIGATORClaire-Marie DHAENENS, MD
University Hospital, Lille
Outcome results
None listed