A novel mutation in the PRPH2 gene in a Chinese pedigree with retinitis pigmentosa and angle-closure glaucoma

Abstract Background Retinitis pigmentosa (RP) is a rare, progressive, and hereditary disorder that leads to the progressive loss of vision and visual field, and in some cases blindness. The specific relationship between RP and glaucoma has been debated for decades. Methods In this study, we examined a Han RP family with concomitant angle-closure glaucoma (ACG), performed an inductive analysis of their clinical features and assistant results, and applied whole-exome sequencing (WES) technology for a molecular diagnosis. Results A novel transversion mutation (c.626 T > A) was identified in the peripherin-2 (PRPH2) gene in the proband, resulting in the substitution of Valine to aspartic acid in codon 209. A full ophthalmic examination showed that the proband with the c.626 T > A mutation had a typical RP manifestation, with close angles; however, the proband’s elder brother, who lacked the novel mutation, had a normal fundus and open angles. Conclusion Our results extend the genetic mutation spectrum of PRPH2 in RP, and provide evidence to support a genetic correlation between RP and ACG.

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A Novel Mutation in the PRPH2 Gene in a Chinese Pedigree with Retinitis Pigmentosa and Angle-closure Glaucoma

10.21203/rs.3.rs-221872/v1 ◽

2021 ◽

Author(s):

Wei-ning Li ◽

Xiu-juan Du ◽

Yu-ting Zhang ◽

Le-yi Wang ◽

Jing Zhu

Keyword(s):

Visual Field ◽

Retinitis Pigmentosa ◽

Novel Mutation ◽

Genetic Mutation ◽

Angle Closure Glaucoma ◽

Angle Closure ◽

The Novel ◽

Progressive Loss ◽

Whole Exome ◽

Transversion Mutation

Abstract Background: Retinitis pigmentosa (RP) is a rare, progressive, and hereditary disorder that leads to the progressive loss of vision and visual field, and in some cases blindness. The specific relationship between RP and glaucoma has been debated for decades.Methods: In this study, we examined a Han RP family with concomitant angle-closure glaucoma (ACG), performed an inductive analysis of their clinical features and assistant results, and applied whole-exome sequencing (WES) technology for a molecular diagnosis. Results: A novel transversion mutation (c.626T>A) was identified in the peripherin-2 (PRPH2) gene in the proband, resulting in the substitution of tyrosine to aspartic acid in codon 209. A full ophthalmic examination showed that the proband with the c.626T>A mutation had a typical RP manifestation, with close angles; however, the proband’s elder brother, who lacked the novel mutation, had a normal fundus and open angles. Conclusion: Our results extend the genetic mutation spectrum of PRPH2 in RP, and provide evidence to support a genetic correlation between RP and ACG.

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RHOMutations (p.W126L and p.A346P) in Two Japanese Families with Autosomal Dominant Retinitis Pigmentosa

Journal of Ophthalmology ◽

10.1155/2014/210947 ◽

2014 ◽

Vol 2014 ◽

pp. 1-10 ◽

Cited By ~ 8

Author(s):

Satoshi Katagiri ◽

Takaaki Hayashi ◽

Masakazu Akahori ◽

Takeshi Itabashi ◽

Jo Nishino ◽

...

Keyword(s):

Molecular Modeling ◽

Retinitis Pigmentosa ◽

Autosomal Dominant ◽

Conformational Transition ◽

Novel Mutation ◽

The Novel ◽

Autosomal Dominant Retinitis Pigmentosa ◽

Modeling Analysis ◽

Whole Exome ◽

The Impact

Purpose. To investigate genetic and clinical features of patients with rhodopsin (RHO) mutations in two Japanese families with autosomal dominant retinitis pigmentosa (adRP).Methods. Whole-exome sequence analysis was performed in ten adRP families. IdentifiedRHOmutations for the cosegregation analysis were confirmed by Sanger sequencing. Ophthalmic examinations were performed to evaluate the RP phenotypes. The impact of theRHOmutation on the rhodopsin conformation was examined by molecular modeling analysis.Results. In two adRP families, we identified twoRHOmutations (c.377G>T (p.W126L) and c.1036G>C (p.A346P)), one of which was novel. Complete cosegregation was confirmed for each mutation exhibiting the RP phenotype in both families. Molecular modeling predicted that the novel mutation (p.W126L) might impair rhodopsin function by affecting its conformational transition in the light-adapted form. Clinical phenotypes showed that patients with p.W126L exhibited sector RP, whereas patients with p.A346P exhibited classic RP.Conclusions. Our findings demonstrated that the novel mutation (p.W126L) may be associated with the phenotype of sector RP. Identification ofRHOmutations is a very useful tool for predicting disease severity and providing precise genetic counseling.

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Interocular Asymmetry of the Visual Field Defects in Newly Diagnosed Normal-tension Glaucoma, Primary Open-angle Glaucoma, and Chronic Angle-closure Glaucoma

Journal of Glaucoma ◽

10.1097/ijg.0b013e3182946553 ◽

2014 ◽

Vol 23 (7) ◽

pp. 455-460 ◽

Cited By ~ 4

Author(s):

Ping Huang ◽

Yan Shi ◽

Xin Wang ◽

Mugen Liu ◽

Chun Zhang

Keyword(s):

Visual Field ◽

Primary Open Angle Glaucoma ◽

Open Angle Glaucoma ◽

Normal Tension Glaucoma ◽

Angle Closure Glaucoma ◽

Angle Closure ◽

Visual Field Defects ◽

Open Angle ◽

Newly Diagnosed ◽

Field Defects

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Visual Field Progression in Patients with Primary Angle-Closure Glaucoma Using Pointwise Linear Regression Analysis

Ophthalmology ◽

10.1016/j.ophtha.2017.02.027 ◽

2017 ◽

Vol 124 (7) ◽

pp. 1065-1071 ◽

Cited By ~ 10

Author(s):

Sushma Verma ◽

Monisha E. Nongpiur ◽

Eray Atalay ◽

Xin Wei ◽

Rahat Husain ◽

...

Keyword(s):

Regression Analysis ◽

Visual Field ◽

Linear Regression ◽

Linear Regression Analysis ◽

Angle Closure Glaucoma ◽

Angle Closure ◽

Visual Field Progression ◽

Primary Angle Closure ◽

Primary Angle Closure Glaucoma

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A Novel COMP Mutated Allele Identified in a Chinese Family with Pseudoachondroplasia

BioMed Research International ◽

10.1155/2021/6678531 ◽

2021 ◽

Vol 2021 ◽

pp. 1-8

Author(s):

Bing-Bing Guo ◽

Jie-Yuan Jin ◽

Zhuang-Zhuang Yuan ◽

Lei Zeng ◽

Rong Xiang

Keyword(s):

Extracellular Matrix ◽

Cartilage Oligomeric Matrix Protein ◽

Matrix Protein ◽

Autosomal Dominant ◽

Novel Mutation ◽

Chinese Family ◽

The Novel ◽

Structure Model ◽

Whole Exome ◽

Nucleotide Mutation

Pseudoachondroplasia (PSACH) is an autosomal dominant skeletal dysplasia with an estimated incidence of ~1/60000 that is characterized by disproportionate short stature, brachydactyly, joint laxity, and early-onset osteoarthritis. COMP encodes the cartilage oligomeric matrix protein, which is expressed predominantly in the extracellular matrix (ECM) surrounding the cells that make up cartilage, ligaments, and tendons. Mutations in COMP are known to give rise to PSACH. In this study, we identified a novel nucleotide mutation (NM_000095.2: c.1317C>G, p.D439E) in COMP responsible for PSACH in a Chinese family by employing whole-exome sequencing (WES) and built the structure model of the mutant protein to clarify its pathogenicity. The novel mutation cosegregated with the affected individuals. Our study expands the spectrum of COMP mutations and further provides additional genetic testing information for other PSACH patients.

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Acute angle closure glaucoma secondary to a luxated lens associated with retinitis pigmentosa

Eye ◽

10.1038/sj.eye.6701527 ◽

2004 ◽

Vol 19 (4) ◽

pp. 472-473 ◽

Cited By ~ 3

Author(s):

M Sira ◽

T Ho

Keyword(s):

Retinitis Pigmentosa ◽

Acute Angle ◽

Angle Closure Glaucoma ◽

Angle Closure ◽

Acute Angle Closure ◽

Acute Angle Closure Glaucoma

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Serum complement component 3, complement component 4 and complement component 1q levels predict progressive visual field loss in older women with primary angle closure glaucoma

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2021-320541 ◽

2022 ◽

pp. bjophthalmol-2021-320541

Author(s):

Shengjie Li ◽

Yichao Qiu ◽

Jian Yu ◽

Mingxi Shao ◽

Yingzhu Li ◽

...

Keyword(s):

Visual Field ◽

Older Women ◽

Statistical Significance ◽

Serum Levels ◽

Complement Component ◽

Angle Closure Glaucoma ◽

Angle Closure ◽

Generalised Additive Model ◽

Primary Angle Closure ◽

Primary Angle Closure Glaucoma

AimTo evaluate the association between serum levels of complement component (C) 3, C4 and C1q and visual field (VF) loss in patients with primary angle closure glaucoma (PACG).MethodsIn this prospective cohort study, a total of 308 patients with PACG were included. The patients were followed up every 6 months (at least 2 years), with clinical examination and VF testing. Based on their sex and age, the subjects were stratified into male and female subgroups, and by age at <60 and ≥60 years per subgroup.ResultsOne hundred twenty-three (39.94%) patients showed glaucoma VF progression. The serum levels of C3, C4 and C1q were significantly lower (p<0.05) in the progression group compared with the non-progression group in the ≥60 years female subgroup. In female patients with age ≥60 years, (1) lower levels of baseline C3 (HR=0.98, p<0.001), C4 (HR=0.96, p=0.01) and C1q levels (HR=0.99, p=0.003) were associated with a greater risk of VF progression; (2) patients with lower C3 levels had significantly (p<0.05) higher rates of VF loss progression, similar to those with lower C4 and lower C1q levels; and (3) the generalised additive model revealed a negative correlation between baseline C3 (p<0.001), C4 (p<0.001) and C1q (p<0.001) levels with the risk of VF progression. No statistical significance was observed in the male (<60 and ≥60 years) and female (<60 years) subgroups.ConclusionDecreased C3, C4 and C1q levels at baseline were significantly associated with a greater risk of VF loss progression only in older women with PACG.

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