A pathogenic in-frame deletion-insertion variant in BEST1 phenocopies Stargardt disease.
JCI Insight
; 7(23)2022 12 08.
Article
em En
| MEDLINE
| ID: mdl-36264634
ABSTRACT
Here, we describe affected members of a 2-generation family with a Stargardt disease-like phenotype caused by a 2-base pair deletion insertion, c.1014_1015delGAinsCT;p.(Trp338_Asn339delinsCysTyr), in BEST1. The variant was identified by whole-exome sequencing, and its pathogenicity was verified through chloride channel recording using WT and transfected mutant HEK293 cells. Clinical examination of both patients revealed similar phenotypes at 2 different disease stages that were attributable to differences in their age at presentation. Hyperautofluorescent flecks along the arcades were observed in the proband, while the affected mother exhibited more advanced retinal pigment epithelium (RPE) loss in the central macula. Full-field electroretinogram testing was unremarkable in the daughter; however, moderate attenuation of generalized cone function was detected in the mother. Results from electrooculogram testing in the daughter were consistent with widespread dysfunction of the RPE characteristic of Best disease. Whole-cell patch-clamp recordings revealed a statistically significant decrease in chloride conductance of the mutant compared with WT cells. This report on a mother and daughter with a BEST1 genotype that phenocopies Stargardt disease broadens the clinical spectrum of BEST1-associated retinopathy.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Bestrofinas
/
Doença de Stargardt
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
Idioma:
En
Revista:
JCI Insight
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos