期刊
GENES
卷 13, 期 4, 页码 -出版社
MDPI
DOI: 10.3390/genes13040617
关键词
achromatopsia; CNGA3; exome sequencing; missense variants; consanguineous families
资金
- National Institute on Deafness and Other Communication Disorders/National Institutes of Health [R01 DC016295]
This study describes the association of CNGA3 missense variants with achromatopsia in three large Pakistani families, resulting in cone photoreceptor dysfunction. Clinical manifestations including thin retina and macular atrophy were observed through fundus examination and OCT imaging.
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 alpha-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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