Five novel dysfunctional variants in the TSPAN12 gene in familial exudative vitreoretinopathy.
Exp Eye Res
; 234: 109574, 2023 09.
Article
en En
| MEDLINE
| ID: mdl-37451565
ABSTRACT
Familial exudative vitreoretinopathy (FEVR) is an inheritable vitreoretinal disease characterized by incomplete retinal vascular development, which often leads to multiple retinal complications and causes severe vision loss in children. We reported the TSPAN12 variants' frequency in a cohort of FEVR and five novel TSPAN12 variants and related clinical features in six Chinese families. Seven hundred thirty-four families' genetic in-house data were reviewed. Whole-exome sequencing (WES) was performed in all probands; Sanger sequencing was conducted in the family members. Five novel variants from six families were noted, and clinical data were collected. Luciferase assays were applied to test the activity of the Norrin/ß-catenin signal caused by the mutant TSPAN12 genes. The frequency of TSPAN12 variants in FEVR is 8.79% (50/569). Five novel variants in TSPAN12 were identified in six families, including two missense variants, c.476G > A(p.Cys159Tyr) and c.81T > G(p.Ser27Arg), two frameshift variants, c.628_629insA(p.Met210Asnfs*42) and c.251delG(p.Gly84Glufs*3) and one nonsense, c.352G > T(p.Glu118*). Low vision, high myopia, nystagmus, and leukocoria are the common symptom at the first presentation. All variants were also predicted as pathogenic in silico. Moreover, the luciferase assay demonstrated that all variants caused severely compromised Norrin/ß-catenin signaling activity. In conclusion, the frequency of TSPAN12 variants in FEVR was 8.79% in our cohort. Five novel variants of TSPAN12 were identified. Moreover, we demonstrated the dysfunction of mutant variants via the downregulation of Norrin/ß-catenin signaling. These findings expanded the genetic and clinical spectrum of FEVR with TSPAN12 variants.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Enfermedades de la Retina
/
Beta Catenina
Tipo de estudio:
Prognostic_studies
Límite:
Child
/
Humans
Idioma:
En
Revista:
Exp Eye Res
Año:
2023
Tipo del documento:
Article
País de afiliación:
China