期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 12, 页码 -出版社
MDPI
DOI: 10.3390/ijms23126868
关键词
cone photoreceptor LWS and MWS opsin genes; haplotype; exonic splicing defect; minigene assay; Blue Cone Monochromacy; Bornholm Eye Disease
资金
- Deutsche Forschungsgemeinschaft [Wi1189/12-1]
Certain combinations of variants in exon 3 of OPN1LW and OPN1MW induce splicing defects and are associated with visual disorders. A novel exon 3 haplotype with a splicing defect has been identified in patients with cone dysfunction. The patients carrying this haplotype showed symptoms of Blue Cone Monochromacy or Bornholm Eye Disease with reduced visual acuity and color vision defects.
Certain combinations of common variants in exon 3 of OPN1LW and OPN1MW, the genes encoding the apo-protein of the long- and middle-wavelength sensitive cone photoreceptor visual pigments in humans, induce splicing defects and have been associated with dyschromatopsia and cone dysfunction syndromes. Here we report the identification of a novel exon 3 haplotype, G-C-G-A-T-T-G-G (referring to nucleotide variants at cDNA positions c.453, c.457, c.465, c.511, c.513, c.521, c.532, and c.538) deduced to encode a pigment with the amino acid residues L-I-V-V-A at positions p.153, p.171, p.174, p.178, and p.180, in OPN1LW or OPN1MW or both in a series of seven patients from four families with cone dysfunction. Applying minigene assays for all observed exon 3 haplotypes in the patients, we demonstrated that the novel exon 3 haplotype L-I-V-V-A induces a strong but incomplete splicing defect with 3-5% of residual correctly spliced transcripts. Minigene splicing outcomes were similar in HEK293 cells and the human retinoblastoma cell line WERI-Rb1, the latter retaining a cone photoreceptor expression profile including endogenous OPN1LW and OPN1MW gene expression. Patients carrying the novel L-I-V-V-A haplotype presented with a mild form of Blue Cone Monochromacy or Bornholm Eye Disease-like phenotype with reduced visual acuity, reduced cone electroretinography responses, red-green color vision defects, and frequently with severe myopia.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据