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Targeted gene under study:

RARB (OMIM: 615524) 

Abstract

RARB-related disorder, also known as MCOPS12, is caused by pathogenic variants in the 
RARB gene. RARB codes for retinoic acid receptor beta, a transcription factor belonging to 
the family of nuclear receptors. This condition is characterized by developmental eye defects 
(including microphthalmia and coloboma), other congenital anomalies (including 
diaphragmatic hernia and heart defects), and global developmental delay with dystonia. 
Although most affected individuals display severe developmental delay and motor 
impairment, some show minimal neurodevelopmental involvement. There is great allelic and 
phenotypic heterogeneity described in this rare and understudied disorder.  
As most reported cases are children, we initiated a natural history study of MCOPS12 to 
better characterize its clinical course across the lifespan. Individuals of any age, from any 
country, carrying pathogenic or likely pathogenic variants in RARB are eligible to participate. 
The study entails annual participant and physician questionnaires, as well as uploading brain 
MRIs and participant videos. Fetal and deceased cases are also eligible to participate, with 
modifications to the study. Our study will lead to the establishment of a framework for the 
development of clinical trials against MCOPS12. 

Coordinating team

Jacques Michaud – principal investigator – Jacques.michaud.med@ssss.gouv.qc.ca  
Valerie Chu – genetic counsellor and study coordinator – valerie.chu.hsj@ssss.gouv.qc.ca

Institution

CHU Sainte-Justine, Montréal, Canada

Specific requirements beyond clinical data and genotype data sharing:

1- Re-analysis of DNA samples: No

2- Resampling of patients: No

3- Linked to a translational/basic research project: Yes