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

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

Abstract Background:Aniridia is a congenital, panocular disease which could affect 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. Distinct mutations at a given site in PAX6 lead to distinctive phenotypic findings. This study aimed to characterize genetic mutations associated with congenital aniridia in a Chinese family.Methods:The proband and family underwent ophthalmologic examinations as well as exome sequencing. Results have been confirmed by Next Generation Sequencing.Results:A novel mutation(c.114_119delinsAATTTCC:p.Pro39llefsTer17)in the PAX6 gene was identified in subjectsⅡ-1, III-1 and III-2 in these family who exhibited complete aniridia and cataract. Proband and the proband’s brother also exhibited glaucoma, high myopia, and foveal hypoplasia.Conclusions：We identified a novel PAX6 frameshift heterozygous deletion mutation in a Chinese family and infered this mutation a probable cause of various eye abnormalities in carriers. Trial registration：We did not do any health-related interventions on the participants.

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.

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 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.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.

Analysis of genotype–phenotype correlations in PAX6-associated aniridia

2020 ◽  
pp. jmedgenet-2019-106172 ◽  
Author(s):  
Tatyana A. Vasilyeva ◽  
Andrey V. Marakhonov ◽  
Anna A. Voskresenskaya ◽  
Vitaly V. Kadyshev ◽  
Barbara Käsmann-Kellner ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Autosomal Dominant ◽  
Regulatory Region ◽  
Missense Mutations ◽  
Loss Of Function ◽  
Exact Test ◽  
Pathogenic Variants ◽  
Different Types ◽  
Congenital Aniridia ◽  
Foveal Hypoplasia

BackgroundAniridia is a severe autosomal dominant panocular disorder associated with pathogenic sequence variants of the PAX6 gene or 11p13 chromosomal aberrations encompassing the coding and/or regulatory regions of the PAX6 gene in a heterozygous state. Patients with aniridia display several ocular anomalies including foveal hypoplasia, cataract, keratopathy, and glaucoma, which can vary in severity and combination.MethodsA cohort of 155 patients from 125 unrelated families with identified point PAX6 pathogenic variants (118 patients) or large chromosomal 11p13 deletions (37 patients) was analyzed. Genetic causes were divided into 6 types. The occurrence of 6 aniridic eye anomalies was analyzed. Fisher’s exact test was applied for 2×2 contingency tables assigning numbers of patients with/without each sign and each type of the PAX6 variants or 11p13 deletions with Benjamini–Hochberg correction. The age of patients with different types of mutation did not differ.ResultsPatients with 3′-cis-regulatory region deletions had a milder aniridia phenotype without keratopathy, nystagmus, or foveal hypoplasia. The phenotypes of the patients with other rearrangements involving 11p13 do not significantly differ from those associated with point pathogenic variants in the PAX6 gene. Missense mutations and genetic variants disrupting splicing are associated with a severe aniridia phenotype and resemble loss-of-function mutations. It is particularly important that in all examined patients, PAX6 mutations were found to be associated with multiple eye malformations. The age of patients with keratopathy, cataract, and glaucoma was significantly higher than the age of patients without these signs.ConclusionWe got clear statistically significant genotype-phenotype correlations in congenital aniridia and evident that aniridia severity indeed had worsened with age.

scholarly journals Cochlear Implantation in a Patient with a Novel POU3F4 Mutation and Incomplete Partition Type-III Malformation

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Xiuhua Chao ◽  
Yun Xiao ◽  
Fengguo Zhang ◽  
Jianfen Luo ◽  
Ruijie Wang ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Cochlear Implantation ◽  
Novel Mutation ◽  
Clinical Manifestations ◽  
Bioinformatic Analysis ◽  
Chinese Family ◽  
Whole Exome ◽  
Novel Variant ◽  
Genetic Features ◽  
The Right

Aims. This study is aimed at (1) analyzing the clinical manifestations and genetic features of a novel POU3F4 mutation in a nonsyndromic X-linked recessive hearing loss family and (2) reporting the outcomes of cochlear implantation in a patient with this mutation. Methods. A patient who was diagnosed as the IP-III malformation underwent cochlear implantation in our hospital. The genetic analysis was conducted in his family, including the whole-exome sequencing combined with Sanger sequencing and bioinformatic analysis. Clinical features, preoperative auditory and speech performances, and postoperative outcomes of cochlear implant (CI) were assessed on the proband and his family. Results. A novel variant c.400_401insACTC (p.Q136LfsX58) in the POU3F4 gene was detected in the family, which was cosegregated with the hearing loss. This variant was absent in 200 normal-hearing persons. The phylogenetic analysis and structure modeling of Pou3f4 protein further confirmed that the novel mutation was pathogenic. The proband underwent cochlear implantation on the right ear at four years old and gained greatly auditory and speech improvement. However, the benefits of the CI declined about three and a half years postoperation. Though the right ear had been reimplanted, the outcomes were still worse than before. Conclusion. A novel frame shift variant c.400_401insACTC (p.Q136LfsX58) in the POU3F4 gene was identified in a Chinese family with X-linked inheritance hearing loss. A patient with this mutation and IP-III malformation could get good benefits from CI. However, the outcomes of the cochlear implantation might decline as the patient grows old.

scholarly journals A Novel Missense Variant of TP63 Heterozygously Present in Split-Hand/Foot Malformation

2020 ◽  
Vol 2020 ◽  
pp. 1-5
Author(s):  
Hao Geng ◽  
Dongdong Tang ◽  
Chuan Xu ◽  
Xiaojin He ◽  
Zhiguo Zhang
Keyword(s):  
Blood Sample ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Peripheral Blood ◽  
Sanger Sequencing ◽  
Missense Variant ◽  
Chinese Family ◽  
Peripheral Blood Sample ◽  
Whole Exome ◽  
Novel Variant

Background. Split-hand/foot malformation (SHFM) is a severe congenital disability mainly characterized by the absence or hypoplasia of the central ray of the hand/foot. To date, several candidate genes associated with SHFM have been identified, including TP63, DLX5, DLX6, FGFR1, and WNT10B. Herein, we report a novel variant of TP63 heterozygously present in affected members of a family with SHFM. Methods. This study investigated a Chinese family, in which the proband and his son suffered from SHFM. The peripheral blood sample of the proband was used to perform whole-exome sequencing (WES) to explore the possible genetic causes of this disease. Postsequencing bioinformatic analyses and Sanger sequencing were conducted to verify the identified variants and parental origins on all family members in the pedigree. Results. By postsequencing bioinformatic analyses and Sanger sequencing, we identified a novel missense variant (NM_003722.4:c.948G>A; p.Met316Ile) of TP63 in this family that results in a substitution of methionine with isoleucine, which is probably associated with the occurrence of SHFM. Conclusion. A novel missense variant (NM_003722.4:c.948G>A; p.Met316Ile) of TP63 in SHFM was thus identified, which may enlarge the spectrum of known TP63 variants and also provide new approaches for genetic counselling of families with SHFM.

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.

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