Delineating the Molecular and Phenotypic Spectrum of the CNGA3-Related Cone Photoreceptor Disorder in Pakistani Families.
Genes (Basel)
; 13(4)2022 03 29.
Article
em En
| MEDLINE
| ID: mdl-35456423
ABSTRACT
Cone photoreceptor dysfunction represents a clinically heterogenous group of disorders characterized by nystagmus, photophobia, reduced central or color vision, and macular dystrophy. Here, we described the molecular findings and clinical manifestations of achromatopsia, a partial or total absence of color vision, co-segregating with three known missense variants of CNGA3 in three large consanguineous Pakistani families. Fundus examination and optical coherence tomography (OCT) imaging revealed myopia, thin retina, retinal pigment epithelial cells loss at fovea/perifovea, and macular atrophy. Combination of Sanger and whole exome sequencing revealed three known homozygous missense variants (c.827A>G, p.(Asn276Ser); c.847C>T, p.(Arg283Trp); c.1279C>T, p.(Arg427Cys)) in CNGA3, the α-subunit of the cyclic nucleotide-gated cation channel in cone photoreceptor cells. All three variants are predicted to replace evolutionary conserved amino acids, and to be pathogenic by specific in silico programs, consistent with the observed altered membrane targeting of CNGA3 in heterologous cells. Insights from our study will facilitate counseling regarding the molecular and phenotypic landscape of CNGA3-related cone dystrophies.
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Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Defeitos da Visão Cromática
/
Células Fotorreceptoras Retinianas Cones
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Humans
País/Região como assunto:
Asia
Idioma:
En
Revista:
Genes (Basel)
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos