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Clinical findings and RS1 genotype in 90 Chinese families with X-linked retinoschisis

PURPOSE: X-linked retinoschisis (XLRS) is an early-onset retinal degenerative disorder caused by mutations in the RS1 gene. The objective of this study was to describe the clinical and genetic findings in 90 unrelated Chinese patients with XLRS. METHODS: All patients underwent clinical examination,...

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Autores principales: Chen, Chunjie, Xie, Yue, Sun, Tengyang, Tian, Lu, Xu, Ke, Zhang, Xiaohui, Li, Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Vision 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155891/
https://www.ncbi.nlm.nih.gov/pubmed/32300273
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author Chen, Chunjie
Xie, Yue
Sun, Tengyang
Tian, Lu
Xu, Ke
Zhang, Xiaohui
Li, Yang
author_facet Chen, Chunjie
Xie, Yue
Sun, Tengyang
Tian, Lu
Xu, Ke
Zhang, Xiaohui
Li, Yang
author_sort Chen, Chunjie
collection PubMed
description PURPOSE: X-linked retinoschisis (XLRS) is an early-onset retinal degenerative disorder caused by mutations in the RS1 gene. The objective of this study was to describe the clinical and genetic findings in 90 unrelated Chinese patients with XLRS. METHODS: All patients underwent clinical examination, including best-corrected visual acuity (BCVA), slit-lamp biomicroscopy, fundus examination, and spectral domain–optical coherence tomography (SD-OCT). A combination of molecular screening methods, including Sanger-DNA sequencing of RS1 and targeted next-generation sequencing (TES), were used to detect mutations. In silico programs were used to analyze the pathogenicity of all the variants. Long-range PCR with subsequent DNA sequencing was employed to find the breakpoints of large deletions. RESULTS: The 90 probands (mean age 17.29±12.94 years; 3–52 years) showed a variety of clinical phenotypes, and their average best correct visual acuity was 0.81±0.48 (logarithm of the minimal angle of resolution, 0–3). Of the 175 eyes analyzed, 140 (80%) had macular retinoschisis, 84 (48%) had peripheral retinoschisis, 28 (16%) had macular atrophy, and five (3%) had a normal macular structure. We identified 68 mutations in this cohort of patients, including 15 novel mutations. Most mutations (65%) were missense; the remaining null mutations included nonsense, splicing effect, frameshift indel, and large genomic DNA deletions. The 62 patients with missense mutations seemed to have relatively milder visual defects than the 28 patients with null mutations. CONCLUSIONS: Patients with RS1 mutations present profound phenotypic variability and show no clear genotype–phenotype correlations. Patients with null mutations tend to have more severe XLRS-related visual defects.
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spelling pubmed-71558912020-04-16 Clinical findings and RS1 genotype in 90 Chinese families with X-linked retinoschisis Chen, Chunjie Xie, Yue Sun, Tengyang Tian, Lu Xu, Ke Zhang, Xiaohui Li, Yang Mol Vis Research Article PURPOSE: X-linked retinoschisis (XLRS) is an early-onset retinal degenerative disorder caused by mutations in the RS1 gene. The objective of this study was to describe the clinical and genetic findings in 90 unrelated Chinese patients with XLRS. METHODS: All patients underwent clinical examination, including best-corrected visual acuity (BCVA), slit-lamp biomicroscopy, fundus examination, and spectral domain–optical coherence tomography (SD-OCT). A combination of molecular screening methods, including Sanger-DNA sequencing of RS1 and targeted next-generation sequencing (TES), were used to detect mutations. In silico programs were used to analyze the pathogenicity of all the variants. Long-range PCR with subsequent DNA sequencing was employed to find the breakpoints of large deletions. RESULTS: The 90 probands (mean age 17.29±12.94 years; 3–52 years) showed a variety of clinical phenotypes, and their average best correct visual acuity was 0.81±0.48 (logarithm of the minimal angle of resolution, 0–3). Of the 175 eyes analyzed, 140 (80%) had macular retinoschisis, 84 (48%) had peripheral retinoschisis, 28 (16%) had macular atrophy, and five (3%) had a normal macular structure. We identified 68 mutations in this cohort of patients, including 15 novel mutations. Most mutations (65%) were missense; the remaining null mutations included nonsense, splicing effect, frameshift indel, and large genomic DNA deletions. The 62 patients with missense mutations seemed to have relatively milder visual defects than the 28 patients with null mutations. CONCLUSIONS: Patients with RS1 mutations present profound phenotypic variability and show no clear genotype–phenotype correlations. Patients with null mutations tend to have more severe XLRS-related visual defects. Molecular Vision 2020-04-11 /pmc/articles/PMC7155891/ /pubmed/32300273 Text en Copyright © 2020 Molecular Vision. http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited, used for non-commercial purposes, and is not altered or transformed.
spellingShingle Research Article
Chen, Chunjie
Xie, Yue
Sun, Tengyang
Tian, Lu
Xu, Ke
Zhang, Xiaohui
Li, Yang
Clinical findings and RS1 genotype in 90 Chinese families with X-linked retinoschisis
title Clinical findings and RS1 genotype in 90 Chinese families with X-linked retinoschisis
title_full Clinical findings and RS1 genotype in 90 Chinese families with X-linked retinoschisis
title_fullStr Clinical findings and RS1 genotype in 90 Chinese families with X-linked retinoschisis
title_full_unstemmed Clinical findings and RS1 genotype in 90 Chinese families with X-linked retinoschisis
title_short Clinical findings and RS1 genotype in 90 Chinese families with X-linked retinoschisis
title_sort clinical findings and rs1 genotype in 90 chinese families with x-linked retinoschisis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155891/
https://www.ncbi.nlm.nih.gov/pubmed/32300273
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