scholarly journals PRPF3-Associated Autosomal Dominant Retinitis Pigmentosa and CYP4V2-Associated Bietti’s Crystalline Corneoretinal Dystrophy Coexist in a Multigenerational Chinese Family

2017 ◽  
Vol 2017 ◽  
pp. 1-10
Author(s):  
Xiaohong Meng ◽  
Qiyou Li ◽  
Hong Guo ◽  
Haiwei Xu ◽  
Shiying Li ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Clinical Features ◽  
Sanger Sequencing ◽  
Mutation Screening ◽  
Retinal Dystrophy ◽  
Family Members ◽  
Large Family ◽  
Chinese Family ◽  
Compound Heterozygous ◽  
Genetic Characteristics

Purpose. To characterize the clinical and molecular genetic characteristics of a large, multigenerational Chinese family showing different phenotypes. Methods. A pedigree consisted of 56 individuals in 5 generations was recruited. Comprehensive ophthalmic examinations were performed in 16 family members affected. Mutation screening of CYP4V2 was performed by Sanger sequencing. Next-generation sequencing (NGS) was performed to capture and sequence all exons of 47 known retinal dystrophy-associated genes in two affected family members who had no mutations in CYP4V2. The detected variants in NGS were validated by Sanger sequencing in the family members. Results. Two compound heterozygous CYP4V2 mutations (c.802-8_810del17insGC and c.992A>C) were detected in the proband who presented typical clinical features of BCD. One missense mutation (c.1482C>T, p.T494M) in the PRPF3 gene was detected in 9 out of 22 affected family members who manifested classical clinical features of RP. Conclusions. Our results showed that two compound heterozygous CYP4V2 mutations caused BCD, and one missense mutation in PRPF3 was responsible for adRP in this large family. This study suggests that accurate phenotypic diagnosis, molecular diagnosis, and genetic counseling are necessary for patients with hereditary retinal degeneration in some large mutigenerational family.

scholarly journals Association of a novel missense mutation in MYO15A with nonsyndromic hearing loss: a case report

2020 ◽  
Author(s):  
Siji Wang ◽  
Ziqi Chen ◽  
Jiaqiu Dai ◽  
Xi Ouyang ◽  
Lin Zhu ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Missense Mutation ◽  
Sanger Sequencing ◽  
Three Dimensional ◽  
Sensorineural Deafness ◽  
Chinese Family ◽  
Common Disease ◽  
Compound Heterozygous ◽  
Nonsyndromic Hearing Loss ◽  
Genetic Sequencing

Abstract Background Hearing loss is a common disease globally, and more than 50% of the cases are genetic. Autosomal recessive nonsyndromic hearing loss (ARNSHL) is one of the most common types of hereditary hearing loss. Here, a novel MYO15A missense mutation was identified in a Chinese family with ARNSHL, using targeted genetic sequencing and Sanger sequencing. Case presentation: A 6-year-old girl with congenital nonsyndromic sensorineural deafness was presented from the First Affiliated hospital of Chongqing Medical University, China. We used targeted region sequencing, Sanger sequencing, functional prediction, and three-dimensional protein structure modeling to identify and verify the genes responsible for deafness in the family. Conclusions We found pathogenic compound heterozygous mutations in MYO15A, including a novel missense mutation, c.6353T > C (p.Leu2118Pro). It could provide help not only for genetic counseling but also for further understanding of the functional role of MYO15A mutations.

scholarly journals Familial autosomal recessive bestrophinopathy: identification of a novel variant in BEST1 gene and the specific metabolomic profile

2020 ◽  
Author(s):  
Panpan Ye ◽  
Jia Xu ◽  
Yueqiu Luo ◽  
Zhitao Su ◽  
ke yao
Keyword(s):  
Missense Mutation ◽  
Sanger Sequencing ◽  
Autosomal Recessive ◽  
Family Members ◽  
Subretinal Fluid ◽  
Angle Closure ◽  
Chinese Family ◽  
Metabolomic Profile ◽  
Metabolic Feature ◽  
Autosomal Recessive Bestrophinopathy

Abstract Background Autosomal recessive bestrophinopathy (ARB) is a retinal degenerative disorder caused by BEST1 mutations with autosomal recessive inheritance. We aim to map a comprehensive genomic and metabolomic profile of a consanguineous Chinese family with ARB. Methods Ophthalmic examinations were performed on the affected patients with ARB. The proband was screened for potential causative mutations in a panel with 256 known retinal disease genes by using target capture sequencing. The related mutation was further validated and segregated in the family members by Sanger sequencing. In silico prediction tools were used for pathogenicity assessment. A UHPLC-MS/MS metabolomic analysis was performed to explore the disease-associated metabolic feature. Results The affected patients from this family were characterized by low vision, the presence of subretinal fluid, macular edema, and hyperopia with coincidental angle closure. DNA sequencing identified a novel missense mutation in the BEST1 gene c.646G>A (p.Val216Ile) of the proband. Sanger sequencing further confirmed the mutation. The missense mutation was co-segregation across the pedigree and predicted to be deleterious by SIFT (0.017). The blood metabolic profiles were highly similar among all family members probably because of the same lifestyle, habitat and genomic background. However, ARB patients presented a significant deregulation of metabolites, such as citric acid, L-Threonic acid, and eicosapentaenoic acid. Conclusions We identified a novel disease-associated variant in the BEST1 gene as well as a disease-specific metabolic feature in familial ARB . Our findings helped improve the understanding of ARB mechanisms.

scholarly journals Familial autosomal recessive bestrophinopathy: identification of a novel variant in BEST1 gene and the specific metabolomic profile

2019 ◽  
Author(s):  
Panpan Ye ◽  
Jia Xu ◽  
Yueqiu Luo ◽  
Zhitao Su ◽  
ke yao
Keyword(s):  
Missense Mutation ◽  
Sanger Sequencing ◽  
Autosomal Recessive ◽  
Family Members ◽  
Subretinal Fluid ◽  
Retinal Disease ◽  
Angle Closure ◽  
Chinese Family ◽  
Disease Genes ◽  
Metabolomic Profile

Abstract BackgroundAutosomal recessive bestrophinopathy (ARB) is a retinal degenerative disorder caused by BEST1 mutations with autosomal recessive inheritance. We aim to map a comprehensive genomic and metabolomic profile of a consanguineous Chinese family with ARB.MethodsOphthalmic examinations were performed on the affected patients with ARB. The proband was screened for potential causative mutations in a panel with 256 known retinal disease genes by using target capture sequencing. The related mutation was further validated and segregated in the family members by Sanger sequencing. In silico prediction tools were used for pathogenicity assessment. A UHPLC-MS/MS metabolomic analysis was performed to explore the disease-associated metabolic feature.ResultsThe affected patients from this family were characterized by low vision, the presence of subretinal fluid, macular edema, and hyperopia with coincidental angle closure. DNA sequencing identified a novel missense mutation in the BEST1 gene c.646G>A (p.Val216Ile) of the proband. Sanger sequencing further confirmed the mutation. The missense mutation was co-segregation across the pedigree and predicted to be deleterious by SIFT (0.017). The blood metabolic profiles were highly similar among all family members probably because of the same lifestyle, habitat and genomic background. However, ARB patients presented a significant deregulation of metabolites, such as citric acid, L-Threonic acid, and eicosapentaenoic acid.ConclusionsWe identified a novel disease-associated variant in the BEST1 gene as well as a disease-specific metabolic feature in familial ARB. Our findings helped improve the understanding of ARB mechanisms.

scholarly journals Novel SOX2 Mutation in Autosomal Dominant Cataract-Microcornea Syndrome

2021 ◽  
Author(s):  
Zhi-Bo Lin ◽  
Jin Li ◽  
Hai-Sen Sun ◽  
A-Yong Yu ◽  
Shi-Hao Chen ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Missense Mutation ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Congenital Cataract ◽  
Autosomal Dominant ◽  
Family Members ◽  
High Mobility ◽  
Chinese Family ◽  
Whole Exome

Abstract Background: Congenital cataract-microcornea syndrome (CCMC) is characterized by the association of congenital cataract and microcornea without any other systemic anomaly or dysmorphism. Although several causative genes have been reported in patients with CCMC, the genetic etiology of CCMC is yet to be clearly understood. Purpose: To unravel the genetic cause of autosomal dominant family with CCMC.Methods: All patients and available family members underwent a comprehensive ophthalmologic clinical examination in the hospital by expert ophthalmologists and carried out to clinically diagnosis. All the patients were screened by whole-exome sequencing and then validated using co-segregation by Sanger sequencing. Results: Four CCMC patients from a Chinese family, and five unaffected family members were enrolled in this study. Using whole-exome sequencing, missense mutation c.295G>T (p.a99s, NM_003106.4) in the SOX2 gene was identified and validated by segregation analysis. In addition, this missense mutation was predicted to be damaging by multiple predictive tools. Variant p.Ala99Ser was located in a conservation high mobility group (HMG)-box domain in SOX2 protein, with a potential pathogenic impact of p.Ala99Ser on protein level.Conclusions: A novel missense mutation (c.295G>T, p.Ala99Ser) in the SOX2 gene was found in this Han Chinese family with congenital cataract and microcornea. Our study firstly determined that mutations in SOX2 were associated with CCMC, warranting further investigations on the pathogenesis of this disorder. This result expands the mutation spectrum of SOX2 and provides useful information to study the molecular pathogenesis of CCMC.

scholarly journals Familial autosomal recessive bestrophinopathy: identification of a novel variant in BEST1 gene and the specific metabolomic profile

2020 ◽  
Author(s):  
Panpan Ye ◽  
Jia Xu ◽  
Yueqiu Luo ◽  
Zhitao Su ◽  
ke yao
Keyword(s):  
Missense Mutation ◽  
Sanger Sequencing ◽  
Autosomal Recessive ◽  
Family Members ◽  
Subretinal Fluid ◽  
Angle Closure ◽  
Chinese Family ◽  
Metabolomic Profile ◽  
Metabolic Feature ◽  
Autosomal Recessive Bestrophinopathy

Abstract Background Autosomal recessive bestrophinopathy (ARB) is a retinal degenerative disorder caused by BEST1 mutations with autosomal recessive inheritance. We aim to map a comprehensive genomic and metabolomic profile of a consanguineous Chinese family with ARB. Methods Ophthalmic examinations were performed on the affected patients with ARB. The proband was screened for potential causative mutations in a panel with 256 known retinal disease genes by using target capture sequencing. The related mutation was further validated and segregated in the family members by Sanger sequencing. In silico prediction tools were used for pathogenicity assessment. A UHPLC-MS/MS metabolomic analysis was performed to explore the disease-associated metabolic feature. Results The affected patients from this family were characterized by low vision, the presence of subretinal fluid, macular edema, and hyperopia with coincidental angle closure. DNA sequencing identified a novel missense mutation in the BEST1 gene c.646G>A (p.Val216Ile) of the proband. Sanger sequencing further confirmed the mutation. The missense mutation was co-segregation across the pedigree and predicted to be deleterious by SIFT (0.017). The blood metabolic profiles were highly similar among all family members probably because of the same lifestyle, habitat and genomic background. However, ARB patients presented a significant deregulation of metabolites, such as citric acid, L-Threonic acid, and eicosapentaenoic acid. Conclusions We identified a novel disease-associated variant in the BEST1 gene as well as a disease-specific metabolic feature in familial ARB . Our findings helped improve the understanding of ARB mechanisms.

scholarly journals Familial autosomal recessive bestrophinopathy: identification of a novel variant in BEST1 gene and the specific metabolomic profile

2020 ◽  
Author(s):  
Panpan Ye ◽  
Jia Xu ◽  
Yueqiu Luo ◽  
Zhitao Su ◽  
ke yao
Keyword(s):  
Missense Mutation ◽  
Sanger Sequencing ◽  
Autosomal Recessive ◽  
Family Members ◽  
Subretinal Fluid ◽  
Angle Closure ◽  
Chinese Family ◽  
Metabolomic Profile ◽  
Metabolic Feature ◽  
Autosomal Recessive Bestrophinopathy

Abstract Background Autosomal recessive bestrophinopathy (ARB) is a retinal degenerative disorder caused by BEST1 mutations with autosomal recessive inheritance. We aim to map a comprehensive genomic and metabolomic profile of a consanguineous Chinese family with ARB. Methods Ophthalmic examinations were performed on the affected patients with ARB. The proband was screened for potential causative mutations in a panel with 256 known retinal disease genes by using target capture sequencing. The related mutation was further validated and segregated in the family members by Sanger sequencing. In silico prediction tools were used for pathogenicity assessment. A UHPLC-MS/MS metabolomic analysis was performed to explore the disease-associated metabolic feature. Results The affected patients from this family were characterized by low vision, the presence of subretinal fluid, macular edema, and hyperopia with coincidental angle closure. DNA sequencing identified a novel missense mutation in the BEST1 gene c.646G>A (p.Val216Ile) of the proband. Sanger sequencing further confirmed the mutation. The missense mutation was co-segregation across the pedigree and predicted to be deleterious by SIFT (0.017). The blood metabolic profiles were highly similar among all family members probably because of the same lifestyle, habitat and genomic background. However, ARB patients presented a significant deregulation of metabolites, such as citric acid, L-Threonic acid, and eicosapentaenoic acid. Conclusions We identified a novel disease-associated variant in the BEST1 gene as well as a disease-specific metabolic feature in familial ARB . Our findings helped improve the understanding of ARB mechanisms.

scholarly journals Novel missense mutation of SASH1 in a Chinese family with dyschromatosis universalis hereditaria

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Lu Cao ◽  
Ruixue Zhang ◽  
Liang Yong ◽  
Shirui Chen ◽  
Hui Zhang ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Sequence Alignment ◽  
Multiple Sequence Alignment ◽  
Molecular Genetic ◽  
Family Members ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Mendelian Inheritance ◽  
Chinese Family ◽  
Multiple Sequence

Abstract Background Dyschromatosis universalis hereditaria (DUH) is a pigmentary dermatosis characterized by generalized mottled macules with hypopigmention and hyperpigmention. ABCB6 and SASH1 are recently reported pathogenic genes related to DUH, and the aim of this study was to identify the causative mutations in a Chinese family with DUH. Methods Sanger sequencing was performed to investigate the clinical manifestation and molecular genetic basis of these familial cases of DUH, bioinformatics tools and multiple sequence alignment were used to analyse the pathogenicity of mutations. Results A novel missense mutation, c.1529G>A, in the SASH1 gene was identified, and this mutation was not found in the National Center for Biotechnology Information Database of Short Genetic Variation, Online Mendelian Inheritance in Man, ClinVar, or 1000 Genomes Project databases. All in silico predictors suggested that the observed substitution mutation was deleterious. Furthermore, multiple sequence alignment of SASH1 revealed that the p.S510N mutation was highly conserved during evolution. In addition, we reviewed the previously reported DUH-related gene mutations in SASH1 and ABCB6. Conclusion Although the affected family members had identical mutations, differences in the clinical manifestations of these family members were observed, which reveals the complexity of the phenotype-influencing factors in DUH. Our findings reveal the mutation responsible for DUH in this family and broaden the mutational spectrum of the SASH1 gene.

scholarly journals Human oocyte maturation arrest caused by a novel missense mutation in TUBB8

2018 ◽  
Vol 46 (9) ◽  
pp. 3759-3764 ◽  
Author(s):  
Jingjing Xiang ◽  
Wei Wang ◽  
Chunfeng Qian ◽  
Jiangyang Xue ◽  
Ting Wang ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Missense Mutation ◽  
Oocyte Maturation ◽  
Clinical Examination ◽  
Sanger Sequencing ◽  
Mutation Screening ◽  
Pcr Amplification ◽  
Human Oocyte ◽  
Maturation Arrest ◽  
Class Viii

Objective To explore the etiology of human oocyte maturation arrest in two infertile Chinese sisters. Methods Clinical examination and genetic testing of all available family members were conducted, and the findings were used to create a pedigree. Mutation screening using PCR amplification and DNA Sanger sequencing of the entire tubulin beta 8 class VIII gene ( TUBB8) including intron–exon boundaries was performed to identify mutations. Results A novel missense TUBB8 mutation (c.1054G > T, p.A352S) in the patient and her elder sister was detected and shown to be associated with oocyte maturation arrest. Conclusion Our findings expand the known mutation spectrum of TUBB8 and provide insights into the etiology of human oocyte maturation arrest.

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.

Probable Novel PSEN1 Gln222Leu Mutation in a Chinese Family with Early-Onset Alzheimer's Disease

2019 ◽  
Vol 16 (8) ◽  
pp. 764-769 ◽  
Author(s):  
Huayuan Wang ◽  
Ruihua Sun ◽  
Yingying Shi ◽  
Mingrong Xia ◽  
Jing Zhao ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Missense Mutation ◽  
Early Onset ◽  
Sanger Sequencing ◽  
Pathogenic Mutation ◽  
Presenilin 1 ◽  
Chinese Family ◽  
Whole Exome ◽  
Early Onset Alzheimer’S Disease

Background: The rate of occurrence of Alzheimer’s disease is increasing around the world. However, there is still no significant breakthrough in the study of its etiology and pathogenesis. Objective: To screen Alzheimer's disease pathogenic genes, which may be conducive to the elucidation of the pathogenic mechanisms of Alzheimer's disease And predict the pathogenicity by various computer software. Method: Clinical and neuroimaging examination, Whole Exome Sequencing, and Sanger sequencing were performed in the proband. Mutation sites were verified in 158 subjects. Results: We reported a proband carrying a probably novel pathogenic mutation, which clinically manifests as progressive memory loss, visual-spatial disorders, apraxia, psychobehavioral disorders, and temperamental and personality changes. Whole Exome Sequencing detected a novel missense mutation at codon 222 (Q222L), which is a heterozygous A to T point mutation at position 665 (c.665A>T) in exon 5 of the presenilin 1 leading to a glutamine-to-leucine substitution. The mutation was also identified by Sanger sequencing in one family member; nevertheless, it was not detected in the other 7 unaffected family members, 50 sporadic Alzheimer's disease patients and 100 control subjects. Conclusion: A novel mutation in exon 5 of the presenilin 1 gene (Gln222Leu) in a Chinese family with early-onset Alzheimer’s disease has been reported, besides， it was predicted that the missense mutation was probably a novel pathogenic mutation that was reported for the first time in a Chinese family with early-onset Alzheimer’s disease.

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