Dataset Information

R102W mutation in the RS1 gene responsible for retinoschisis and recurrent glaucoma.

ABSTRACT:

Aim

To identify the mutations in RS1 gene associated with typical phenotype of X-linked juvenile retinoschisis (XLRS) and a rare condition of concomitant glaucoma.

Methods

Complete ophthalmic examinations were performed in the proband. The coding regions of the RS1 gene that encode retinoschisin were amplified by polymerase chain reaction and directly sequenced.

Results

The proband showed a typical phenotype of XLRS with large peripheral retinal schisis in both eyes, involving the macula and combined with foveal cystic change, reducing visual acuity. A typical phenotype of recurrent glaucoma with high intraocular pressure (IOP) and reduced visual field was also demonstrated with the patient. Mutation analysis of RS1 gene revealed R102W (c.304C>T) mutations in the affected male, and his mother was proved to be a carrier with the causative mutation and another synonymous polymorphism (c.576C>CT).

Conclusion

We identified the genetic variations of a Chinese family with typical phenotype of XLRS and glaucoma. The severe XLRS phenotypes associated with R102W mutations reveal that the mutation determines a notable alteration in the function of the retinoschisin protein. Identification of the disease-causing mutation is beneficial for future clinical references.

SUBMITTER: Huang XF

PROVIDER: S-EPMC3951554 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

R102W mutation in the RS1 gene responsible for retinoschisis and recurrent glaucoma.

Huang Xiu-Feng XF Tu Chang-Sen CS Xing Dong-Jun DJ Gan De-Kang DK Xu Ge-Zhi GZ Jin Zi-Bing ZB

International journal of ophthalmology 20140218 1

<h4>Aim</h4>To identify the mutations in RS1 gene associated with typical phenotype of X-linked juvenile retinoschisis (XLRS) and a rare condition of concomitant glaucoma.<h4>Methods</h4>Complete ophthalmic examinations were performed in the proband. The coding regions of the RS1 gene that encode retinoschisin were amplified by polymerase chain reaction and directly sequenced.<h4>Results</h4>The proband showed a typical phenotype of XLRS with large peripheral retinal schisis in both eyes, involv ...[more]

PMID: 24634885

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Project description:The purpose of the present study was to assess the clinical characteristics of X-linked retinoschisis (XLRS) in a Chinese family over a 7-year period with the aim of identifying possible genetic mutations associated with this disease. A total of 2 male siblings from a family with XLRS were followed up for 7 years and the best-corrected visual acuity and data obtained using slit-lamp microscopy, indirect ophthalmoscopy, fundus photography, spectral domain-optical coherence tomography (OCT), fundus autofluorescence and fundus fluorescence (FFA) and multifocal electroretinograms (ERG) were examined. The coding regions of the retinoschisin 1 (RS1) gene were amplified by PCR and sequenced directly. The proband exhibited blurred vision at 12 years old and was indicated to exhibit a typical phenotype of XLRS at 30 years old. The elder brother exhibited blurred vision at 11 years old and was diagnosed with XLRS at 33 years old. There was no change in the best-corrected visual acuities in the two patients over the 7 years. The OCT results suggested that there were intraretinal cysts and macular atrophy in the eyes of the older sibling, whilst a 'spoke-wheel' pattern was present in the macula of the younger sibling. In addition, OCT examination revealed foveal schisis. FFA analysis indicated a hyperfluorescent signal in the central macula. Multifocal ERG recordings indicated that responses were markedly reduced in the central and outer rings bilaterally. The central retinal thickness of the younger sibling increased but the central retinal thickness of the older sibling was not changed during the 7 years. Sequencing analysis revealed that the mutation was c.366G>A (p.Trp122*) in exon 5 of Xp22.1. Gene mutation analysis indicated that the affected male siblings harbored a Trp122* (c.366G>A) mutation, while the patients' mother was demonstrated to be a heterozygous carrier of the pathogenic mutation. To conclude, the present study discovered a novel XLRS mutation in a Chinese family, where the Trp122* mutation caused a significant change in the function of the RS1 protein. Over the 7 years of observation, although the vision was not significantly impaired in the two patients examined, the central retinal thickness of the younger sibling increased but the central retinal thickness of the older sibling was not altered.

Project description:PURPOSE: To determine the clinical features and to identify mutations in the retinoschisis gene (RS1) in ten patients with X-linked retinoschisis (XLRS). METHODS: Ten male patients from nine Polish families were included in this study. Ophthalmologic examinations, including optical coherence tomography (OCT) and full-field electroretinography (ERG), were performed in all affected boys. The entire coding region encompassing six exons of the RS1 gene was amplified with PCR and directly sequenced in all the patients. RESULTS: All affected individuals showed typical retinoschisis signs and symptoms, and all appeared to have a mutation in the RS1 gene. Seven different mutations were identified, including two novel missense substitutions: c.176G>C (p.Cys59Ser), c.451T>A (p.Tyr151Asp); one novel nonsense substitution: c.218C>A (p.Ser73*); and one novel frameshift mutation: c.354_355delCA (p.Asp118Glufs*2). We also found two missense substitutions that had been previously described: c.214G>A (p.Glu72Lys) and c.626G>T (p.Arg209Leu) and one known splice site mutation in intron 5: c.522+1G>T (IVS5+1G>T). CONCLUSIONS: This study provides the first molecular genetic characteristics of patients with juvenile retinoschisis from the previously unexplored Polish population. We investigated the molecular background of XLRS in ten boys. The present study reports for the first time four novel mutations, including two missense substitutions, one nonsense substitution, and one frameshift deletion. One of these substitutions and 2-bp deletion created stop codons. Moreover, we described three substitutions that had been previously reported (one is a splicing mutation). Further genetic characterization of Polish patients with XLRS will be helpful in understanding the worldwide spectrum of RS1 mutations. Despite the mutation heterogeneity found in a small group of our patients, they presented a relatively uniform clinical picture. Identifying the causative mutation is helpful in confirming diagnosis and counseling, but cannot provide prognostic data.

Dataset Information

R102W mutation in the RS1 gene responsible for retinoschisis and recurrent glaucoma.

Aim

Methods

Results

Conclusion

Publications

R102W mutation in the RS1 gene responsible for retinoschisis and recurrent glaucoma.

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