scholarly journals A novel 4.25 kb heterozygous deletion in PAX6 in a Chinese Han family with congenital aniridia combined with cataract and nystagmus

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tianwei Qian ◽  
Chong Chen ◽  
Caihua Li ◽  
Qiaoyun Gong ◽  
Kun Liu ◽  
...  
Keyword(s):  
Genetic Defect ◽  
Family Members ◽  
Anterior Segment ◽  
Chinese Family ◽  
The Novel ◽  
Heterozygous Deletion ◽  
Chinese Han ◽  
Indirect Ophthalmoscopy ◽  
Normal People ◽  
Congenital Aniridia

Abstract Background The aim of this study is to identify the genetic defect in a Chinese family with congenital aniridia combined with cataract and nystagmus. Methods Complete ophthalmic examinations, including slit-lamp biomicroscopy, dilated indirect ophthalmoscopy, anterior segment photography, and anterior segment optical coherence tomography (OCT) were performed. Blood samples were collected from all family members and genomic DNA was extracted. Genome sequencing was performed in all family members and Sanger sequencing was used to verify variant breakpoints. Results All the thirteen members in this Chinese family, including seven patients and six normal people, were recruited in this study. The ophthalmic examination of affected patients in this family was consistent with congenital aniridia combined with cataract and nystagmus. A novel heterozygous deletion (NC_000011.10:g.31802307_31806556del) containing the 5′ region of PAX6 gene was detected that segregated with the disease. Conclusion We detected a novel deletion in PAX6 responsible for congenital aniridia in the affected individuals of this Chinese family. The novel 4.25 kb deletion in PAX6 gene of our study would further broaden the genetic defects of PAX6 associated with congenital aniridia.

A Novel 4.25kb Deletion in PAX6 in A Chinese Han Family with Congenital Aniridia Combined with Cataract and Nystagmus

2021 ◽  
Author(s):  
Tianwei Qian ◽  
Chong Chen ◽  
Caihua Li ◽  
Qiaoyun Gong ◽  
Kun Liu ◽  
...  
Keyword(s):  
Genetic Defect ◽  
Family Members ◽  
Anterior Segment ◽  
Chinese Family ◽  
The Novel ◽  
Slit Lamp ◽  
Heterozygous Deletion ◽  
Chinese Han ◽  
Normal People ◽  
Congenital Aniridia

Abstract Background: The aim of this study is to identify the genetic defect in a Chinese family with congenital aniridia combined with cataract and nystagmus.Methods: Complete ophthalmic examinations, including slit-lamp biomicroscopy, dilatedindirect ophthalmoscopy, anterior segment photography, and anterior segment optical coherence tomography (OCT) were performed. Blood samples were collected from all family members and genomic DNA was extracted. Genome sequencing was performed in all family members and Sanger sequencing was used to verify variant breakpoints.Results: All the thirteen members in this Chinese family, including seven patients and six normal people, were recruited in this study. The ophthalmic examination of affected patients in this family was consistent with congenital aniridia combined with cataract and nystagmus. A novel heterozygous deletion (NC_000011.10:g.31802307_31806556del) containing the 5’ region of PAX6 gene was detected that segregated with the disease. Conclusion: We detected a novel deletion in PAX6 responsible for congenital aniridia in the affected individuals of this Chinese family. The novel 4.25kb deletion in PAX6 gene of our study would further broaden the genetic defects of PAX6 associated with congenital aniridia.

scholarly journals A Novel Mutation in the Kringle IV Domain of LPA gene leading to Familial Hyperlipoproteinemia

2019 ◽  
Author(s):  
Youran Li ◽  
Xinyue Zhang ◽  
Yizhong Wang ◽  
Fan Gong ◽  
Xiaofei Yu ◽  
...  
Keyword(s):  
Novel Mutation ◽  
Genetic Defect ◽  
Clinical Manifestations ◽  
Chinese Family ◽  
Heterozygous Deletion ◽  
Chinese Han ◽  
Combined Use ◽  
The Family ◽  
Number Variation ◽  
Generation Sequencing

Abstract Background This study aims to investigate the clinical characterization and causative genetic defect of a four-generation Chinese Han family with hyperlipoproteinemia. Methods The combined use of next-generation sequencing and qPCR technique was performed to investigate genetic pathology of familial hyperlipoproteinemia. Results The clinical manifestations of the family members include hyperlipoproteinemia, early-onset hypertension, coronary heart disease, lipoma, cerebral infarction and even sudden death, and a novel heterozygous deletion of 3-16 exon of LPA gene was identified to be causative for the symptoms in the family. Conclusions A novel deletion in the LPA gene was identified in a Chinese family associated with hyperlipoproteinemia, which expands the spectrum of the LPA mutation and its associated phenotype. Keywords Copy number variation; Hyperlipoproteinemia; Kringle IV; Lipoprotein(a); LPA;

scholarly journals Novel MFSD8 Variants in a Chinese Family with Nonsyndromic Macular Dystrophy

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Qin Xiang ◽  
Yanna Cao ◽  
Hongbo Xu ◽  
Zhijian Yang ◽  
Liang Tang ◽  
...  
Keyword(s):  
Family Members ◽  
Major Facilitator Superfamily ◽  
Chinese Family ◽  
Macular Dystrophy ◽  
Compound Heterozygous ◽  
The Novel ◽  
Pathogenic Variants ◽  
Compound Heterozygous Variants ◽  
Major Facilitator ◽  
Mfsd8 Gene

Purpose. To identify the molecular etiology of a Chinese family with nonsyndromic macular dystrophy. Methods. Ophthalmic examinations were performed, and genomic DNA was extracted from available family members. Whole exome sequencing of two members (the proband and her unaffected mother) and Sanger sequencing in available family members were performed to screen potential pathogenic variants. Results. Novel compound heterozygous variants, c.1066C>T (p.Pro356Ser) and c.1102+2T>C, in the major facilitator superfamily domain containing 8 gene (MFSD8) were suspected to be involved in this family’s macular dystrophy phenotype. The novel c.1066C>T variant in the MFSD8 gene probably resulted in substitution of serine for proline at the 356th residue and was predicted to be “uncertain significance” through in silico analyses. The novel c.1102+2T>C variant in the MFSD8 gene was likely to affect the splicing form and predicted to be “pathogenic.” Conclusion. The novel compound heterozygous variants, c.1066C>T (p.Pro356Ser) and c.1102+2T>C, in the MFSD8 gene are likely responsible for the isolated macular dystrophy phenotype in this family. This study enlarged the MFSD8 gene mutant spectrum and might provide more accurate genetic counseling for this family.

scholarly journals Recurrent PAX 6 mutation in a Chinese family with congenital aniridia, progressive cataracts and mental retardation

2018 ◽  
Vol 30 (1) ◽  
pp. 181-188
Author(s):  
Dou-Dou Chen ◽  
Tao Yang ◽  
Si-Quan Zhu
Keyword(s):  
Mental Retardation ◽  
Family Members ◽  
Gene Mutations ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Pathological Feature ◽  
Phosphate Backbone ◽  
Symptom Complex ◽  
Congenital Aniridia ◽  
And Control

Background: One prominent pathological feature of congenital aniridia is hypoplasia of the iris, often accompanied by other eye abnormalities. The objective of this study is to identify gene mutations responsible for autosomal dominance in a Chinese family with congenital aniridia, progressive cataracts and mental retardation. Methods: A total of 11 family members, including 6 affected and 5 unaffected individuals were recruited. Whole exome sequencing was performed on the proband and Sanger sequencing was applied to identify the causal mutation in the other family members and control samples. Results: A heterozygous mutation, c. 112delC (p. Arg38fs) in PAX 6, was identified in the family that was associated with congenital aniridia, progressive cataracts and mental retardation. The mutation was exclusively observed in all affected individuals but not in unaffected family members or unrelated healthy controls without aniridia recruited from Beijing Tongren Hospital. Bioinformatics analysis indicated that the mutation c. 112delC (p. Arg38fs) in PAX 6 affected sugar phosphate backbone construction, leading to half reduction of the full-length protein. Other symptoms such as lens opacity, keratitis, lens dislocation, ciliary body hypoplasia, foveal hypoplasia and mental development retardation were also observed in this family. Conclusion: These results provided a new insight into the effects of PAX 6 as a mutational hotspot, with a symptom complex that includes congenital aniridia, progressive cataracts and mental retardation. These findings suggested the cognitive treatment of PAX 6-mutated individuals could be considered earlier clinically, combined with medication or surgery of congenital aniridia and progressive cataracts.

scholarly journals Detection of a novel PAX6 mutation in a Chinese family with multiple ocular abnormalities

2021 ◽  
Author(s):  
Junyi Ouyang ◽  
Ziyan Cai ◽  
Yinjie Guo ◽  
Fen Nie ◽  
Mengdan Cao ◽  
...  
Keyword(s):  
Novel Mutation ◽  
Chinese Family ◽  
Genetic Mutations ◽  
Anterior Chamber Angle ◽  
Loss Of Function ◽  
Heterozygous Deletion ◽  
Congenital Aniridia ◽  
Foveal Hypoplasia ◽  
Generation Sequencing ◽  
Pax6 Mutation

Abstract Background: Aniridia is a congenital,panocular disease affecting the cornea,anterior chamber angle,iris,lens,retina and optic nerve.PAX6 loss-of-function mutations were the most common cause of aniridia.Mutations throughout the PAX6 gene have been linked to a range of ophthalmic abnormalities,with distinct mutations at a given site within this gene leading to distinct phenotypic findings.This study aimed to characterize genetic mutations associated with congenital aniridia in a Chinese family. Methods: The proband and the proband’s brother of this family underwent comprehensive ophthalmologic examinations as well as exome sequencing,with Next Generation Sequencing being used to confirm these results. Results: A novel mutation(c.114_119delinsAATTTCC:p.Pro39fs)in the PAX6 gene was identified in subjects III-2 and III-3 in these family,and both of these subjects exhibited completeaniridia,cataracts,glaucoma,high myopia,and foveal hypoplasia. Conclusions We identified a novel PAX6 frameshift heterozygous deletion mutation in a Chinese family and determined that this mutation was a probable cause of various eye abnormalities in carriers.

scholarly journals Detection of a novel PAX6 mutation in a Chinese family with multiple ocular abnormalities

2020 ◽  
Author(s):  
Junyi Ouyang ◽  
Ziyan Cai ◽  
Yinjie Guo ◽  
Fen Nie ◽  
Mengdan Cao ◽  
...  
Keyword(s):  
Novel Mutation ◽  
Chinese Family ◽  
Pax6 Gene ◽  
Anterior Chamber Angle ◽  
Loss Of Function ◽  
Heterozygous Deletion ◽  
Congenital Aniridia ◽  
Foveal Hypoplasia ◽  
Generation Sequencing ◽  
Pax6 Mutation

Abstract Background: Aniridia is a congenital, panocular disease affecting the cornea, anterior chamber angle, iris, lens, retina and optic nerve. PAX6 loss-of-function mutations were the most common cause of aniridia .Mutations throughout the PAX6 gene have been linked to a range of ophthalmic abnormalities, with distinct mutations at a given site within this gene leading to distinct phenotypic findings.This s tudy aimed to characterize genetic mutations associated with congenital aniridia in a Chinese family. Methods: The proband and the proband’s brother of this family underwent comprehensive ophthalmologic examinations as well as exome sequencing, with Next Generation Sequencing being used to confirm these results. Results: A novel mutation (c.114_119delinsAATTTCC:p.Pro39fs) in the PAX6 gene was identified in subjects III-2 and III-3 in these family, and both of these subjects exhibited complete aniridia, cataracts, glaucoma, high myopia, and foveal hypoplasia. Conclusions: We identified a novel PAX6 frameshift heterozygous deletion mutation in a Chinese family and determined that this mutation was a probable cause of various eye abnormalities in carriers.

Identification of a novel PHEX mutation in a Chinese family with X-linked hypophosphatemic rickets using exome sequencing

2015 ◽  
Vol 396 (1) ◽  
pp. 27-33 ◽  
Author(s):  
Lamei Yuan ◽  
Song Wu ◽  
Hongbo Xu ◽  
Jingjing Xiao ◽  
Zhijian Yang ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Genetic Defect ◽  
Hypophosphatemic Rickets ◽  
Chinese Family ◽  
Dental Development ◽  
Serum Phosphate Level ◽  
Loss Of Function ◽  
Hearing Impairments ◽  
Chinese Han ◽  
Teeth Abnormalities

Abstract Familial hypophosphatemic rickets (HR), the most common inherited form of rickets, is a group of inherited renal phosphate wasting disorders characterized by growth retardation, rickets with bone deformities, osteomalacia, poor dental development, and hypophosphatemia. The purpose of this study was to identify the genetic defect responsible for familial HR in a four-generation Chinese Han pedigree by exome sequencing and Sanger sequencing. Clinical features include skeletal deformities, teeth abnormalities, hearing impairments and variable serum phosphate level in patients of this family. A novel deletion mutation, c.1553delT (p.F518Sfs*4), was identified in the X-linked phosphate regulating endopeptidase homolog gene (PHEX). The mutation is predicted to result in prematurely truncated and loss-of-function PHEX protein. Our data suggest that exome sequencing is a powerful tool to discover mutation(s) in HR, a disorder with genetic and clinical heterogeneity. The findings may also provide new insights into the cause and diagnosis of HR, and have implications for genetic counseling and clinical management.

scholarly journals Detection of a novel PAX6 variant in a Chinese family with multiple ocular abnormalities

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Junyi Ouyang ◽  
Ziyan Cai ◽  
Yinjie Guo ◽  
Fen Nie ◽  
Mengdan Cao ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Chinese Family ◽  
Anterior Chamber Angle ◽  
Loss Of Function ◽  
Heterozygous Deletion ◽  
Whole Exome ◽  
Novel Variant ◽  
Health Related ◽  
Congenital Aniridia ◽  
Foveal Hypoplasia

Abstract Background Aniridia is a congenital, panocular disease that can affect the cornea, anterior chamber angle, iris, lens, retina and optic nerve. PAX6 loss-of-function variants are the most common cause of aniridia, and variants throughout the gene have been linked to a range of ophthalmic abnormalities. Furthermore, particular variants at a given site in PAX6 lead to distinct phenotypes. This study aimed to characterize genetic variants associated with congenital aniridia in a Chinese family. Methods The proband and family underwent ophthalmologic examinations. DNA was sampled from the peripheral blood of all 6 individuals, and whole-exome sequencing was performed. Sanger sequencing was used to verify the variant in this family members. Results A novel variant (c.114_119delinsAATTTCC: p.Pro39llefsTer17) in the PAX6 gene was identified in subjects II-1, III-1 and III-2, who exhibited complete aniridia and cataracts. The proband and the proband’s brother also had glaucoma, high myopia, and foveal hypoplasia. Conclusions We identified that a novel PAX6 frameshift heterozygous deletion variant is the predominant cause of aniridia in this Chinese family. Trial registration We did not perform any health-related interventions for the participants.

scholarly journals Detection of a  novel PAX6 mutation  in a Chinese family with multiple ocular abnormalities

2020 ◽  
Author(s):  
Junyi Ouyang ◽  
Ziyan Cai ◽  
Yinjie Guo ◽  
Fen Nie ◽  
Mengdan Cao ◽  
...  
Keyword(s):  
Novel Mutation ◽  
Chinese Family ◽  
Genetic Mutations ◽  
Anterior Chamber Angle ◽  
Loss Of Function ◽  
Heterozygous Deletion ◽  
Congenital Aniridia ◽  
Foveal Hypoplasia ◽  
Generation Sequencing ◽  
Pax6 Mutation

Abstract Background Aniridia is a congenital,panocular disease affecting the cornea,anterior chamber angle,iris,lens,retina and optic nerve.PAX6 loss-of-function mutations were the most common cause of aniridia.Mutations throughout the PAX6 gene have been linked to a range of ophthalmic abnormalities,with distinct mutations at a given site within this gene leading to distinct phenotypic findings.This study aimed to characterize genetic mutations associated with congenital aniridia in a Chinese family.MethodsThe proband and the proband’s brother of this family underwent comprehensive ophthalmologic examinations as well as exome sequencing,with Next Generation Sequencing being used to confirm these results.Results A novel mutation(c.114_119delinsAATTTCC:p.Pro39fs)in the PAX6 gene was identified in subjects III-2 and III-3 in these family,and both of these subjects exhibited completeaniridia,cataracts,glaucoma,high myopia,and foveal hypoplasia.Conclusions We identified a novel PAX6 frameshift heterozygous deletion mutation in a Chinese family and determined that this mutation was a probable cause of various eye abnormalities in carriers.

scholarly journals Identification of a novel CHN1 p.(Phe213Val) variant in a large Han Chinese family with congenital Duane retraction syndrome

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Tai-Cheng Zhou ◽  
Wen-Hua Duan ◽  
Xiao-Lin Fu ◽  
Qin Zhu ◽  
Li-Yun Guo ◽  
...  
Keyword(s):  
Genetic Defect ◽  
Family Members ◽  
The United States ◽  
Chinese Family ◽  
Causative Gene ◽  
Functional Studies ◽  
Retraction Syndrome ◽  
Activation Assay ◽  
Tertiary Protein Structure ◽  
Duane Retraction Syndrome

Abstract Duane retraction syndrome (DRS) is a neuromuscular dysfunction of the eyes. Although many causative genes of DRS have been identified in Europe and the United States, few reports have been published in regard to Chinese DRS. The aim of the present study was to explore the genetic defect of DRS in a Chinese family. Exome sequencing was used to identify the disease-causing gene for the two affected family members. Ophthalmic and physical examinations, as well as genetic screenings for variants in chimerin 1 (CHN1), were performed for all family members. Functional analyses of a CHN1 variant in 293T cells included a Rac-GTP activation assay, α2-chimaerin translocation assay, and co-immunoprecipitation assay. Genetic analysis revealed a NM_001822.7: c.637T > G variant in the CHN1 gene, which resulted in the substitution of a highly conserved C1 domain with valine at codon 213 (NP_001813.1: p.(Phe213Val)) (ClinVar Accession Number: SCV001335305). In-silico analysis revealed that the p.(Phe213Val) substitution affected the protein stability and connections among the amino acids of CHN1 in terms of its tertiary protein structure. Functional studies indicated that the p.(Phe213Val) substitution reduced Rac-GTP activity and enhanced membrane translocation in response to phorbol-myristoyl acetate (PMA). Together with previous studies, our present findings demonstrate that CHN1 may be an important causative gene for different ethnicities with DRS.

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