scholarly journals A novel missense variant c.G644A (p.G215E) of the RPGR gene in a Chinese family causes X-linked retinitis pigmentosa

2019 ◽  
Vol 39 (10) ◽  
Author(s):  
Jiewen Fu ◽  
Jingliang Cheng ◽  
Qi Zhou ◽  
Chunli Wei ◽  
Hanchun Chen ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Expression Patterns ◽  
Missense Variant ◽  
Vital Role ◽  
Chinese Family ◽  
The Novel ◽  
Rna Seq ◽  
Targeted Next Generation Sequencing ◽  
Retinal Tissue ◽  
Eye Tissues

Abstract The mutations in patients with X-linked retinitis pigmentosa (xlRP) have not been well described in the Chinese population. In the present study, a five-generation Chinese retinitis pigmentosa (RP) family was recruited; targeted next-generation sequencing (TGS) was used to identify causative genes and Sanger sequencing for co-segregation. RNA-seq data analysis and revere transcriptional-polymerase chain reaction (RT-PCR) were applied to investigate gene expression patterns of RP GTPase regulator (RPGR) in human and Rpgr in mouse. A novel, hemizygous, deleterious and missense variant: c.G644A (p.G215E) in the RPGR gene (NM_000328.2) exon 7 of X-chromosome was identified in the proband, which was co-segregated with the clinical phenotypes in this family. RNA-seq data showed that RPGR is ubiquitously expressed in 27 human tissues with testis in highest, but no eye tissues data. Then the expressions for Rpgr mRNA in mice including eye tissues were conducted and showed that Rpgr transcript is ubiquitously expressed very highly in retina and testis, and highly in other eye tissues including lens, sclera, and cornea; and expressed highly in the six different developmental times of retinal tissue. Ubiquitous expression in different tissues from eye and very high expression in the retina indicated that RPGR plays a vital role in eye functions, particularly in retina. In conclusion, our study is the first to indicate that the novel missense variant c.G644A (p.G215E) in the RPGR gene might be the disease-causing mutation in this xlRP family, expanding mutation spectrum. These findings facilitate better understanding of the molecular pathogenesis of this disease; provide new insights for genetic counseling and healthcare.

A novel variant in PAX6 as the cause of aniridia in a Chinese family

2020 ◽  
Author(s):  
Xin Jin ◽  
Wei Liu ◽  
HouBin Huang
Keyword(s):  
Nonsense Mutation ◽  
Novel Mutation ◽  
Causative Mutation ◽  
Chinese Family ◽  
The Novel ◽  
Targeted Next Generation Sequencing ◽  
Iris Defect ◽  
The Family ◽  
Novel Variant ◽  
Pax6 Mutation

Abstract Background: Aniridia is a kind of congenital human panocular anomaly, which is related to PAX6 commonly. Methods: A Chinese Aniridia pedigree underwent ophthalmic examinations, including visual acuity, slit lamp and fundoscopy examination. The targeted next-generation sequencing of Aniridia genes was used to identify the causative mutation. Results: A novel heterozygous PAX6 nonsense mutation c.619A>T (p.K207*) was identified in the Chinese autosomal dominant family with aniridia. Phenotypes related to the novel mutation include nystagmus, iris defect, cataract and absence of macular fovea. Conclusion: The novel nonsense mutation in PAX6 was responsible for aniridia phenotype in the family. which expands the spectrum of the PAX6 mutation and its associated phenotype.

scholarly journals Transcriptomic analysis of Verbena bonariensis roots in response to cadmium stress

BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Meng-qi Wang ◽  
Zhen-yu Bai ◽  
Ya-fang Xiao ◽  
Yan Li ◽  
Qing-lin Liu ◽  
...  
Keyword(s):  
Cell Structure ◽  
Expression Patterns ◽  
Enrichment Analysis ◽  
Cadmium Stress ◽  
The Novel ◽  
Rna Seq ◽  
Cd Stress ◽  
Ros Scavenging ◽  
Molecular Alterations ◽  
Cd Tolerance

Abstract Background Cadmium (Cd) is a serious heavy metal (HM) soil pollutant. To alleviate or even eliminate HM pollution in soil, environmental-friendly methods are applied. One is that special plants are cultivated to absorb the HM in the contaminated soil. As an excellent economical plant with ornamental value and sound adaptability, V. bonariensis could be adapted to this very situation. In our study, the Cd tolerance in V. bonariensis was analyzed as well as an overall analysis of transcriptome. Results In this study, the tolerance of V. bonariensis to Cd stress was investigated in four aspects: germination, development, physiological changes, and molecular alterations. The results showed that as a non-hyperaccumulator, V. bonariensis did possess the Cd tolerance and the capability to concentration Cd. Under Cd stress, all 237, 866 transcripts and 191, 370 unigenes were constructed in the transcriptome data of V. bonariensis roots. The enrichment analysis of gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway revealed that differentially expressed genes (DEGs) under Cd stress were predominately related to cell structure, reactive oxygen species (ROS) scavenging system, chelating reaction and secondary metabolites, transpiration and photosynthesis. DEGs encoding lignin synthesis, chalcone synthase (CHS) and anthocyanidin synthase (ANS) were prominent in V. bonariensis under Cd stress. The expression patterns of 10 DEGs, validated by quantitative real-time polymerase chain reaction (qRT-PCR), were in highly accordance with the RNA-Sequence (RNA-Seq) results. The novel strategies brought by our study was not only benefit for further studies on the tolerance of Cd and functional genomics in V. bonariensis, but also for the improvement molecular breeding and phytoremediation.

scholarly journals Identifying core biological processes distinguishing human eye tissues with precise systems-level gene expression analyses and weighted correlation networks

2017 ◽  
Author(s):  
John M Bryan ◽  
Temesgen D Fufa ◽  
Kapil Bharti ◽  
Brian P Brooks ◽  
Robert B Hufnagel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Patterns ◽  
Mouse Retina ◽  
Human Tissues ◽  
Biological Processes ◽  
Rna Seq ◽  
Human Eye ◽  
Correlation Networks ◽  
Eye Tissues ◽  
Study Gene Expression

AbstractThe human eye is built from several specialized tissues which direct, capture, and pre-process information to provide vision. The gene expression of the different eye tissues has been extensively profiled with RNA-seq across numerous studies. Large consortium projects have also used RNA-seq to study gene expression patterning across many different human tissues, minus the eye. There has not been an integrated study of expression patterns from multiple eye tissues compared to other human body tissues. We have collated all publicly available healthy human eye RNA-seq datasets as well as dozens of other tissues. We use this fully integrated dataset to probe the biological processes and pan expression relationships between the cornea, retina, RPE-choroid complex, and the rest of the human tissues with differential expression, clustering, and GO term enrichment tools. We also leverage our large collection of retina and RPE-choroid tissues to build the first human weighted gene correlation networks and use them to highlight known biological pathways and eye gene disease enrichment. We also have integrated publicly available single cell RNA-seq data from mouse retina into our framework for validation and discovery. Finally, we make all these data, analyses, and visualizations available via a powerful interactive web application (https://eyeintegration.nei.nih.gov/).

scholarly journals A novel variant in PAX6  as the cause of aniridia in a Chinese family

2020 ◽  
Author(s):  
Xin Jin ◽  
Wei Liu ◽  
HouBin Huang ◽  
Linghui Qv ◽  
Wenqin Xv
Keyword(s):  
Autosomal Dominant ◽  
Novel Mutation ◽  
Causative Mutation ◽  
Chinese Family ◽  
The Novel ◽  
Slit Lamp ◽  
Targeted Next Generation Sequencing ◽  
Novel Variant ◽  
Foveal Hypoplasia ◽  
Generation Sequencing

Abstract Background: Aniridia is a kind of congenital human pan-ocular anomaly, which is related to PAX6 commonly.Methods: The ophthalmic examinations including visual acuity, slit lamp and fundoscopy examination were performed in a Chinese aniridia pedigree. The targeted next-generation sequencing of aniridia genes was used to identify the causative mutation.Results: A novel heterozygous PAX6 nonsense mutation c.619A>T (p.K207*) was identified in the Chinese autosomal dominant family with aniridia. Phenotype related to the novel mutation included nystagmus, keratopathy, absence of iris, cataract and foveal hypoplasia.Conclusion: The novel nonsense variation in PAX6 was the cause of aniridia in this family, which expanded the spectrum of the PAX6 mutation.

scholarly journals Transcriptomic analysis of Verbena bonariensis roots in response to cadmium stress

2019 ◽  
Author(s):  
Meng-qi Wang ◽  
Zhen-yu Bai ◽  
Ya-fang Xiao ◽  
Yan Li ◽  
Qing-lin Liu ◽  
...  
Keyword(s):  
Cell Structure ◽  
Expression Patterns ◽  
Enrichment Analysis ◽  
Cadmium Stress ◽  
The Novel ◽  
Rna Seq ◽  
Cd Stress ◽  
Ros Scavenging ◽  
Molecular Alterations ◽  
Cd Tolerance

Abstract Background: Cadmium (Cd) is a serious heavy metal (HM) soil pollutant. To alleviate or even eliminate HM pollution in soil, environmental-friendly methods are applied. One is that special plants are cultivated to absorb the HM in the contaminated soil. As an excellent economical plant with ornamental value and sound adaptability, V.bonariensis could be adapted to this very situation. In our study, the Cd tolerance in V.bonariensis was analyzed as well as overall analysis of transcriptome. Results: In this study, the tolerance of V.bonariensis to Cd stress was investigated in four aspects: germination, development, pysiological changes, and molecular alterations. The results showed that as a non-hyperaccumulator, V. bonariensis did possess the Cd tolerance and the capability to concentration Cd. Under Cd stress, all 237,866 transcripts and 191,370 unigenes were constructed in the transcriptome data of V.bonariensis roots . The enrichment analysis of gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway revealed that differentially expressed genes (DEGs) under Cd stress were predominately related to cell structure, reactive oxygen species (ROS) scavenging system, chelating reaction and secondary metabolites, transpiration and photosynthesis. DEGs encoding lignin synthesis, chalcone synthase (CHS) and anthocyanidin synthase (ANS) were prominent in V. bonariensis under Cd stress. The expression patterns of 10 DEGs, validated by quantitative real-time polymerase chain reaction (qRT-PCR), were in highly accordance with the RNA-Sequence (RNA-Seq) results. The novel strategies brought by our study was not only benefit for further studies on the tolerance of Cd and functional genomics in V. bonariensis , but also for the improvement molecular breeding and phytoremediation.

scholarly journals Transcriptomic analysis of Verbena bonariensis roots in response to cadmium stress

2019 ◽  
Author(s):  
Meng-qi Wang ◽  
Zhen-yu Bai ◽  
Ya-fang Xiao ◽  
Yan Li ◽  
Qing-lin Liu ◽  
...  
Keyword(s):  
Cell Structure ◽  
Expression Patterns ◽  
Enrichment Analysis ◽  
Cadmium Stress ◽  
The Novel ◽  
Rna Seq ◽  
Cd Stress ◽  
Ros Scavenging ◽  
Molecular Alterations ◽  
Cd Tolerance

Abstract Background: Cadmium (Cd) is a serious heavy metal (HM) soil pollutant. To alleviate or even eliminate HM pollution in soil, environmental-friendly methods are applied. One is that special plants are cultivated to absorb the HM in the contaminated soil. As an excellent economical plant with ornamental value and sound adaptability, V.bonariensis could be adapted to this very situation. In our study, the Cd tolerance in V.bonariensis was analyzed as well as overall analysis of transcriptome. Results: In this study, the tolerance of V.bonariensis to Cd stress was investigated in four aspects: germination, development, pysiological changes, and molecular alterations. The results showed that as a non-hyperaccumulator, V. bonariensis did possess the Cd tolerance and the capability to concentration Cd. Under Cd stress, all 237,866 transcripts and 191,370 unigenes were constructed in the transcriptome data of V.bonariensis roots . The enrichment analysis of gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway revealed that differentially expressed genes (DEGs) under Cd stress were predominately related to cell structure, reactive oxygen species (ROS) scavenging system, chelating reaction and secondary metabolites, transpiration and photosynthesis. DEGs encoding lignin synthesis, chalcone synthase (CHS) and anthocyanidin synthase (ANS) were prominent in V. bonariensis under Cd stress. The expression patterns of 10 DEGs, validated by quantitative real-time polymerase chain reaction (qRT-PCR), were in highly accordance with the RNA-Sequence (RNA-Seq) results. The novel strategies brought by our study was not only benefit for further studies on the tolerance of Cd and functional genomics in V. bonariensis , but also for the improvement molecular breeding and phytoremediation.

scholarly journals A novel variant in PAX6 as the cause of aniridia in a Chinese family

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
X Jin ◽  
W Liu ◽  
LH Qv ◽  
WQ X ◽  
HB Huang
Keyword(s):  
Autosomal Dominant ◽  
Novel Mutation ◽  
Causative Mutation ◽  
Chinese Family ◽  
The Novel ◽  
Slit Lamp ◽  
Targeted Next Generation Sequencing ◽  
Novel Variant ◽  
Foveal Hypoplasia ◽  
Generation Sequencing

Abstract Background Aniridia is a kind of congenital human pan-ocular anomaly, which is related to PAX6 commonly. Methods The ophthalmic examinations including visual acuity, slit lamp and fundoscopy examination were performed in a Chinese aniridia pedigree. The targeted next-generation sequencing of aniridia genes was used to identify the causative mutation. Results A novel heterozygous PAX6 nonsense mutation c.619A > T (p.K207*) was identified in the Chinese autosomal dominant family with aniridia. Phenotype related to the novel mutation included nystagmus, keratopathy, absence of iris, cataract and foveal hypoplasia. Conclusions The novel nonsense variation in PAX6 was the cause of aniridia in this family, which expanded the spectrum of the PAX6 mutation.

scholarly journals Autosomal Recessive Retinitis Pigmentosa Associated with Three Novel REEP6 Variants in Chinese Population

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 537
Author(s):  
Lujia Zhang ◽  
Ya Li ◽  
Litao Qin ◽  
Yu Wu ◽  
Bo Lei
Keyword(s):  
Retinitis Pigmentosa ◽  
Autosomal Recessive ◽  
Cultured Cells ◽  
Missense Variant ◽  
Chinese Families ◽  
Targeted Next Generation Sequencing ◽  
Novel Variants ◽  
Next Generation Sequencing Ngs ◽  
Computational Predictions

Retinitis pigmentosa 77 is caused by mutations of REEP6 (MIM: 609346), which encodes a protein for the development of photoreceptors. Our study was to identify disease-causing variants in three Chinese families using targeted next-generation sequencing (NGS). Multiple lines of computational predictions combined with in vitro cellular experiments were applied to evaluate the pathogenicity of the newly found variants. Three novel variants in REEP6, including one missense variant, c.268G>C, one frameshift variant, c.468delC, and one splicing variant, c.598+1G>C, were found, while c.268G>C was detected in all probands. The three variants were classified as likely pathogenic by the American College of Medical Genetics and Genomics (ACMG). REEP6 variant proteins c.268G>C and c.468delC in cultured cells destabilized the REEP6 protein and induced intracellular inclusions. Our data suggested that REEP6 c.268G>C may be a recurrent causative variant in Chinese autosomal recessive retinitis pigmentosa patients.

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

2018 ◽  
Vol 51 (5) ◽  
pp. 2445-2455 ◽  
Author(s):  
Lisha Yang ◽  
Jiewen Fu ◽  
Jingliang Cheng ◽  
Chunli Wei ◽  
Qi Zhou ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Developmental Stages ◽  
Expression Patterns ◽  
Chinese Family ◽  
Causative Gene ◽  
Familial Exudative Vitreoretinopathy ◽  
Targeted Next Generation Sequencing ◽  
Reverse Transcription Pcr ◽  
Candidate Mutation ◽  
Novel Variant

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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