Next-generation sequencing-based molecular diagnosis of 35 Hispanic retinitis pigmentosa probands

Zhang, Qi; Xu, Min; Verriotto, Jennifer; Li, Yumei; Wang, Hui; Gan, Lin; Lam, Byron L.; Chen, Rui

doi:10.1038/srep32792

Cited by 42 publications

(33 citation statements)

References 36 publications

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“…After quality assessment, more than 97% of the billions of bases were aligned to the human reference sequences and, among those, billions of bases were recovered with a 10‐fold coverage target region. Then, causative mutations were identified by automatic variant calling, filtering and annotation pipeline in the capture sequencing data . SIFT, Polyphen 2, LRT, MutationTaster, MutationAssessor and dbNSFP were used to filter out non‐pathogenic population variations, which were not annotated in any of the above public databases and were prioritized for further confirmation and characterization.…”

Section: Resultsmentioning

confidence: 99%

“…Here, we applied targeted next‐generation sequencing (TGS) technology, the most available ‎and promising method available, to identify a novel, homologous mutation of CDHR1 gene in a Chinese family with autosomal recessive retinal dystrophy, extending the gene's mutation spectrum.…”

Section: Introductionmentioning

confidence: 99%

“…CDHR1 is a photoreceptor-specific cadherin, 9 and immunoprecipitation studies showed that CDHR1 are also found in complexes with PROM1 and actin filaments, playing a critical role in photoreceptor disk morphogenesis. 10 Here, we applied targeted next-generation sequencing (TGS) technology, the most available and promising method available, [11][12][13][14][15][16] to identify a novel, homologous mutation of CDHR1 gene in a Chinese family with autosomal recessive retinal dystrophy, extending the gene's mutation spectrum.…”

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confidence: 99%

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A novel, homozygous nonsense variant of the CDHR1 gene in a Chinese family causes autosomal recessive retinal dystrophy by NGS‐based genetic diagnosis

Cheng

et al. 2018

J Cellular Molecular Medi

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Retinal dystrophy is an inherited, heterogeneous, chronic and progressive disorder of visual functions. The mutations of patients with autosomal recessive retinal retinopathy cone‐and‐rod dysfunction and macular dystrophy have not been well described in the Chinese population. In this study, a three‐generation Chinese retinal dystrophy family was recruited. Ophthalmic examinations were performed. Targeted next generation sequencing (TGS) was used to identify causative genes, and Sanger sequencing was conducted to verify candidate mutations and co‐segregation. Reverse transcription (RT)‐PCR was applied to investigate the spatial and temporal expression patterns of cdhr1 gene in mouse. A novel, homozygous, deleterious and nonsense variant (c.T1641A; p.Y547*) in the CDHR1 gene was identified in the family with autosomal recessive retinal dystrophy, which was co‐segregated with the clinical phenotypes in this family. RT‐PCR analysis revealed that cdhr1 is ubiquitously expressed in eye, particularly very high expression in retina; high expression in lens, sclera, and cornea; and high expression in brain. In conclusion, our study is the first to indicate that the novel homozygous variant c.T1641A (p.Y547*) in the CHDR1 gene might be the disease‐causing mutation for retinal dystrophy in our patient, extending its mutation spectrums. These findings further the understanding of the molecular pathogenesis of this disease and provide new insights for diagnosis as well as new implications for genetic counselling.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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A novel, homozygous nonsense variant of the CDHR1 gene in a Chinese family causes autosomal recessive retinal dystrophy by NGS‐based genetic diagnosis

Cheng

et al. 2018

J Cellular Molecular Medi

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“…The capture Agilent probes were used as in previously published studies [11,12,14,22] with a retinal disease capture panel that included FEVR-related genes: NDP, FZD4, LRP5, TSPAN12, ZNF408, CTNNB1, RCBTB1, and KIF11. In brief, 2 μg of the extracted proband gDNA was randomly sheared by sonication into 300-500 bp fragments.…”

Section: Capture Panel Design and Target Sequencingmentioning

confidence: 99%

“…To identify the disease-causing gene and to identify mutation, TES analyses were performed on the gDNA sample of the proband from pedigree M362 DNA, according to the instructions for Illumina pairedend libraries (Illumina, Inc., San Diego, CA) as reported previously [11,12,14]. The capture Agilent probes were used as in previously published studies [11,12,14,22] with a retinal disease capture panel that included FEVR-related genes: NDP, FZD4, LRP5, TSPAN12, ZNF408, CTNNB1, RCBTB1, and KIF11.…”

Section: Capture Panel Design and Target Sequencingmentioning

confidence: 99%

A Novel Variant of the FZD4 Gene in a Chinese Family Causes Autosomal Dominant Familial Exudative Vitreoretinopathy

Yang

Cheng

et al. 2018

Cell Physiol Biochem

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Background/Aims: Familial exudative vitreoretinopathy (FEVR) is a complex hereditary eye disorder characterized by incomplete development of the retinal vasculature, thereby affecting retinal angiogenesis. Methods: In this study, a Chinese autosomal dominant FEVR pedigree was recruited. Ophthalmic examinations were performed, targeted next-generation sequencing was used to identify the causative gene, and Sanger sequencing was conducted to verify the candidate mutation. Co-segregation analysis was performed to evaluate pathogenicity. Semi-quantitative reverse transcription-PCR was applied to investigate the spatial and temporal expression patterns of the frizzled class receptor 4 (FZD4) gene in the mouse. Results: A novel heterozygous, deleterious variant of the FZD4 gene, c.A749G (p.Y250C), was identified in this FEVR pedigree, which co-segregated with the clinical phenotype. The amino acid tyrosine (Y) is highly conserved both orthologously and paralogously. The FZD4 gene was highly expressed in the retina, sclera of the eye, ovary, kidney, and liver; ubiquitously expressed in other tissues; and highly expressed in 6 different developmental stages/times of retinal tissue. Conclusion: Our study is the first to identify that the novel heterozygous variant c.A749G (p.Y250C) in the FZD4 gene may be the disease-causing mutation in this FEVR family, extending its mutation spectrum. These findings further our understanding of the molecular pathogenesis of FEVR and will facilitate the development of methods for the diagnosis, prevention, and genetic counseling of this disease.

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Comprehensive analysis of the PRPF31 gene in retinitis pigmentosa patients: Four novel Alu ‐mediated copy number variations at the PRPF31 locus

Chen

Gao

et al. 2022

Human Mutation

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Retinitis pigmentosa (RP) is a monogenic disease characterized by irreversible degeneration of the retina. PRPF31, the second most common causative gene of autosomal dominant RP, frequently harbors copy number variations (CNVs), but the underlying mechanism is unclear. In this study, we summarized the phenotypic and genotypic characteristics of 18 RP families (F01−F18) with variants in PRPF31. The prevalence of PRPF31 variants in our cohort of Chinese RP families was 1.7% (18/ 1024). Seventeen different variants in PRPF31 were detected, including eight novel variants. Notably, four novel CNVs encompassing PRPF31, with a proportion of 22.2% (4/18), were validated to harbor gross deletions involving Alu/Alu-mediated rearrangements (AAMRs) in the same orientation. Among a total of 12 CNVs of PRPF31 with breakpoints mapped on nucleotide-resolution, 10 variants (83.3%) were presumably mediated by Alu elements. Furthermore, we described the correlation between the genotypes and phenotypes in PRPF31-related RP. Our findings expand the mutational spectrum of the PRPF31 gene and provide strong evidence that Alu elements of PRPF31 probably contribute to the susceptibility to genomic rearrangement in this locus.

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Next-generation sequencing-based molecular diagnosis of 35 Hispanic retinitis pigmentosa probands

Cited by 42 publications

References 36 publications

A novel, homozygous nonsense variant of the CDHR1 gene in a Chinese family causes autosomal recessive retinal dystrophy by NGS‐based genetic diagnosis

A novel, homozygous nonsense variant of the CDHR1 gene in a Chinese family causes autosomal recessive retinal dystrophy by NGS‐based genetic diagnosis

A Novel Variant of the FZD4 Gene in a Chinese Family Causes Autosomal Dominant Familial Exudative Vitreoretinopathy

Comprehensive analysis of the PRPF31 gene in retinitis pigmentosa patients: Four novel Alu ‐mediated copy number variations at the PRPF31 locus

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