Clinical and Genetic Spectrum of OPN1LW/OPN1MW-Associated Disorders in a Chinese Cohort: Contribution of Long-Read Sequencing
- 1State Key Laboratory of Complex Severe and Rare Diseases, Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, No. 1, Shuai Fu Yuan, Beijing 100730, China
Abstract
The highly homologous OPN1LW/OPN1MW gene cluster poses substantial challenges for molecular diagnosis. We retrospectively enrolled 12 male patients from 10 unrelated Chinese families with clinically suspected X-linked cone-opsin disorder, all of whom were confirmed to carry disease-associated variants or haplotypes in the OPN1LW/OPN1MW gene cluster. Clinical records, retinal imaging, electrophysiology, and available ocular biometry were analyzed together with short-read sequencing, Sanger validation, copy-number analysis, and Oxford Nanopore long-read sequencing for three cases with incomplete short-read resolution. Clinical subgroups included blue cone monochromacy (n = 5), X-linked cone dystrophy (n = 4), Bornholm eye disease (n = 2), and isolated color-vision deficiency (n = 1). Molecular results encompassed sequence variants, exon dosage alterations, a 51.8 kb deletion involving the locus control region, and exon 3 haplotypes. Long-read sequencing defined the deletion breakpoint in one case and the exon 3 haplotypes in two. In one boy with an X-linked cone dystrophy phenotype, the mean binocular axial length increased from 25.36 mm to 28.47 mm between 1.80 and 6.24 years of age. Our findings demonstrate the complementary utility of multimodal molecular assays and heterogeneous phenotypes of cone-opsin disorders, with sustained childhood axial elongation reported only as a single-case observation.
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BibTeX
@article{wei2026clinical,
title = {{Clinical and Genetic Spectrum of OPN1LW/OPN1MW-Associated Disorders in a Chinese Cohort: Contribution of Long-Read Sequencing}},
author = {Xing Wei and Yamei Li and Hui Li and Wuyi Li and Yunyu Zhou and Ruifang Sui},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219705},
url = {https://www.mdpi.com/1422-0067/27/21/9705},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Clinical and Genetic Spectrum of OPN1LW/OPN1MW-Associated Disorders in a Chinese Cohort: Contribution of Long-Read Sequencing
AU - Xing Wei
AU - Yamei Li
AU - Hui Li
AU - Wuyi Li
AU - Yunyu Zhou
AU - Ruifang Sui
PY - 2026
DA - 2026/10/29
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219705
UR - https://www.mdpi.com/1422-0067/27/21/9705
AB - The highly homologous OPN1LW/OPN1MW gene cluster poses substantial challenges for molecular diagnosis. We retrospectively enrolled 12 male patients from 10 unrelated Chinese families with clinically suspected X-linked cone-opsin disorder, all of whom were confirmed to carry disease-associated variants or haplotypes in the OPN1LW/OPN1MW gene cluster. Clinical records, retinal imaging, electrophysiology, and available ocular biometry were analyzed together with short-read sequencing, Sanger validation, copy-number analysis, and Oxford Nanopore long-read sequencing for three cases with incomplete short-read resolution. Clinical subgroups included blue cone monochromacy (n = 5), X-linked cone dystrophy (n = 4), Bornholm eye disease (n = 2), and isolated color-vision deficiency (n = 1). Molecular results encompassed sequence variants, exon dosage alterations, a 51.8 kb deletion involving the locus control region, and exon 3 haplotypes. Long-read sequencing defined the deletion breakpoint in one case and the exon 3 haplotypes in two. In one boy with an X-linked cone dystrophy phenotype, the mean binocular axial length increased from 25.36 mm to 28.47 mm between 1.80 and 6.24 years of age. Our findings demonstrate the complementary utility of multimodal molecular assays and heterogeneous phenotypes of cone-opsin disorders, with sustained childhood axial elongation reported only as a single-case observation.
SN - 1422-0067
ER -