Loss of Function of RIMS2 Causes a Syndromic Congenital Cone-Rod Synaptic Disease with Neurodevelopmental and Pancreatic Involvement.
Am J Hum Genet
; 106(6): 859-871, 2020 06 04.
Article
in En
| MEDLINE
| ID: mdl-32470375
ABSTRACT
Congenital cone-rod synaptic disorder (CRSD), also known as incomplete congenital stationary night blindness (iCSNB), is a non-progressive inherited retinal disease (IRD) characterized by night blindness, photophobia, and nystagmus, and distinctive electroretinographic features. Here, we report bi-allelic RIMS2 variants in seven CRSD-affected individuals from four unrelated families. Apart from CRSD, neurodevelopmental disease was observed in all affected individuals, and abnormal glucose homeostasis was observed in the eldest affected individual. RIMS2 regulates synaptic membrane exocytosis. Data mining of human adult bulk and single-cell retinal transcriptional datasets revealed predominant expression in rod photoreceptors, and immunostaining demonstrated RIMS2 localization in the human retinal outer plexiform layer, Purkinje cells, and pancreatic islets. Additionally, nonsense variants were shown to result in truncated RIMS2 and decreased insulin secretion in mammalian cells. The identification of a syndromic stationary congenital IRD has a major impact on the differential diagnosis of syndromic congenital IRD, which has previously been exclusively linked with degenerative IRD.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Eye Diseases, Hereditary
/
Night Blindness
/
GTP-Binding Proteins
/
Genetic Diseases, X-Linked
/
Loss of Function Mutation
/
Myopia
/
Nerve Tissue Proteins
Type of study:
Diagnostic_studies
/
Etiology_studies
Limits:
Adult
/
Child
/
Child, preschool
/
Female
/
Humans
/
Male
Country/Region as subject:
Africa
/
Asia
/
Europa
Language:
En
Journal:
Am J Hum Genet
Year:
2020
Document type:
Article
Affiliation country:
Francia