Identification and molecular characterization of two recurrent missense mutations in the RS1 gene in two families with X-linked retinoschisis from North India.
Am J Med Genet A
; 191(10): 2524-2535, 2023 10.
Article
en En
| MEDLINE
| ID: mdl-37317958
ABSTRACT
X-linked retinoschisis (XLR) is a rare medical condition that involves in the splitting of neurosensory layers and the impairment of vision in the retina. In majority of the XLR cases, pathogenic variants in Retinoschisin 1 (RS1) gene have been implicated in males with an early age of onset during early childhood. In the present study, we have recruited two North Indian families having multiple affected male members, who were diagnosed with XLR. The entire protein-coding region of RS1 was screened by PCR-Sanger sequencing and two recurrent pathogenic variants (p.I81N and p.R102Q) were unraveled. The in vitro study of these variants demonstrated the aggregation of mutant RS1 within the endoplasmic reticulum. Furthermore, mutant forms of this protein showed significant intracellular retention, which was evident by the absence of retinoschisin protein fractions in the extracellular media. These inferences were also supported by extensive bioinformatics analysis of the mutants, which showed dramatic conformational changes in the local structure of retinoschisin. Thus, our study suggests that the identified pathogenic variants interfere with proper protein folding, leading to anomalous structural changes ultimately resulting in intracellular retention of retinoschisin within the retina.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Retinosquisis
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Child, preschool
/
Humans
/
Male
País/Región como asunto:
Asia
Idioma:
En
Revista:
Am J Med Genet A
Asunto de la revista:
GENETICA MEDICA
Año:
2023
Tipo del documento:
Article
País de afiliación:
India