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.

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 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 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):  
Autosomal Dominant ◽  
Novel Mutation ◽  
Causative Mutation ◽  
Chinese Family ◽  
The Novel ◽  
Slit Lamp ◽  
Targeted Next Generation Sequencing ◽  
Iris Defect ◽  
Novel Variant ◽  
Generation Sequencing

Abstract Background: Aniridia is a kind of congenital human panocular anomaly, which is related to PAX6 commonly.Methods: The ophthalmic examinations including visual acuity, slit lamp and fundoscopy examination were preformed 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. Phenotypes related to the novel mutation include nystagmus, iris defect, cataract and absence of macular fovea.Conclusion: The novel nonsense variation in PAX6 was the cause of aniridia in this family, which expands the spectrum of the PAX6 mutation and its associated phenotype.

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 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.

scholarly journals Mutations in PIKFYVE cause autosomal dominant congenital cataract

2021 ◽  
Author(s):  
Shaoyi Mei ◽  
Yi Wu ◽  
Yan Wang ◽  
Yubo Cui ◽  
Miao Zhang ◽  
...  
Keyword(s):  
Congenital Cataract ◽  
Autosomal Dominant ◽  
Kinase Domain ◽  
Dominant Negative ◽  
Chinese Family ◽  
Bafilomycin A1 ◽  
Atpase Inhibitor ◽  
Causative Gene ◽  
Whole Exome ◽  
Autosomal Dominant Congenital Cataract

Congenital cataract, an ocular disease predominantly occurring within the first decade of life, is one of the leading causes of blindness in children. Through whole exome sequencing of a Chinese family with congenital cataract, we identified a disease-causing mutation (p.G1943E) in PIKFYVE, which affecting the PIP kinase domain of the PIKfyve protein. We demonstrated that heterozygous/homozygous disruption of PIKfyve kinase domain, instead of overexpression of PIKFYVEG1943E in zebrafish mimicked the cataract defect in human patients, suggesting that haploinsufficiency, rather than dominant-negative inhibition of PIKfyve activity caused the disease. Phenotypical analysis of pikfyve zebrafish mutants revealed that loss of Pikfyve caused aberrant vacuolation (accumulation of Rab7+Lc3+ amphisomes) in lens cells, which was significantly alleviated by treatment with the V-ATPase inhibitor bafilomycin A1 (Baf-A1). Collectively, we identified PIKFYVE as a novel causative gene for congenital cataract and demonstrated the potential application of Baf-A1 in treatment of congenital cataract.

The acid invertase gene family is involved in internode elongation in Phyllostachys heterocycla cv. pubescens

2020 ◽  
Vol 40 (9) ◽  
pp. 1217-1231 ◽  
Author(s):  
Xiaoqin Guo ◽  
Hongjun Chen ◽  
Yue Liu ◽  
Wei Chen ◽  
Yeqing Ying ◽  
...  
Keyword(s):  
Developmental Stages ◽  
Expression Patterns ◽  
Constitutive Expression ◽  
Amino Acid Identity ◽  
Internode Elongation ◽  
Fast Growing ◽  
Reverse Transcription Pcr ◽  
High Amino Acid ◽  
Phyllostachys Heterocycla ◽  
Vegetative And Reproductive Growth

Abstract Acid invertases (INVs) play a pivotal role in both vegetative and reproductive growth of plants. However, their possible functions in fast-growing plants such as bamboo are largely unknown. Here, we report the molecular characterization of acid INVs in Phyllostachys heterocycla cv. pubescens, a fast-growing bamboo species commercially grown worldwide. Nine acid INVs (PhINVs), including seven cell wall INVs (PhCWINV1, PhCWINV2, PhCWINV3, PhCWINV4, PhCWINV5, PhCWINV6 and PhCWINV7) and two vacuolar INVs (PhVINV11 and PhVINV12) were isolated. Bioinformatic analyses demonstrated that they all share high amino acid identity with other INVs from different plant species and contain the motifs typically conserved in acid INV. Enzyme activity assays revealed a significantly higher INV activity in the fast-growing tissues, such as the elongating internodes of stems. Detailed quantitative reverse-transcription PCR analyses showed various expression patterns of PhINVs at different developmental stages of the elongating stems. With the exception of PhCWINV6, all PhINVs were ubiquitously expressed in a developmental-specific manner. Further studies in Arabidopsis exhibited that constitutive expression of PhCWINV1, PhCWINV4 or PhCWINV7 increased the biomass production of transgenic plants, as indicated by augmented plant heights and shoot dry weights than the wild-type plants. All these results suggest that acid INVs play a crucial role in the internode elongation of P. heterocycla cv. pubescens and would provide valuable information for the dissection of their exact biological functions in the fast growth of bamboo.

scholarly journals A novel variant of IHH in a Chinese family with brachydactyly type 1

2019 ◽  
Author(s):  
Qi Yang ◽  
Jin Wang ◽  
Xiaoxian Tian ◽  
Fei Chen ◽  
Jing Lan ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Missense Variant ◽  
Chinese Family ◽  
Indian Hedgehog ◽  
Autosomal Dominant Disorder ◽  
Pathogenic Variants ◽  
Whole Exome ◽  
Novel Variant ◽  
Active Fragment

Abstract Brachydactyly type A1(BDA-1) is an autosomal dominant disorder which is caused by heterozygous pathogenic variants in a specific region of the N-terminal active fragment of Indian Hedgehog ( IHH ). The disorder is mainly characterized by shortening or missing of the middle phalanges. The following study revealed a novel heterozygous missense variant c.299A>G (p.D100G) at the mutational hotspot of IHH gene after performing whole-exome sequencing in the proband of a Chinese family with BDA-1. The variant co-segregated with BDA-1 in the pedigree, showed 100% penetrance for phalange phenotype with variable expressivity. This finding expanded the variants on IHH gene which contribute to the cause of BDA-1.

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