A Missense Mutation in OPA1 Causes Dominant Optic Atrophy in a Chinese Family

Background. To investigate the genetic causes and clinical characteristics of dominant optic atrophy (DOA) in a Chinese family. Methods. A 5-generation pedigree of 35 family members including 12 individuals affected with DOA was recruited from Shenzhen Eye Hospital, China. Four affected family members and one unaffected family member were selected for whole exome sequencing. Sanger sequencing was used to confirm and screen the identified mutation in 18 members of the family. The disease-causing mutation was identified by bioinformatics analysis and confirmed by segregation analysis. The clinical characteristics of the family members were analyzed. Results. A heterozygous missense mutation (c.1313A>G, p.D438G) in optic atrophy 1 (OPA1) was identified in 10 individuals affected with DOA in this family. None of the unaffected family members had the mutation. Patients in this family had vision loss since they were children or adolescence. The visual acuity decreased progressively to hand movement, except for one patient (IV-12) who had relatively good vision of 20/30 and 20/28. The fundus typically manifested as optic disc pallor. The visual fields, optical coherence tomography, and visual evoked potential suggested variable degree of abnormality in patients. Patients who had a history of cigarette smoking and alcohol drinking had more severe clinical manifestations. Conclusions. Our results suggest that the p.D438G mutation in OPA1 causes optic atrophy in this family. The patients who carried the mutation demonstrated heterogeneous clinical manifestations in this family. This is the first report on the c.1313A>G (p.D438G) mutation of OPA1 in a Chinese family affected with DOA.

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

BMC Medical Genomics ◽

10.1186/s12920-021-01014-w ◽

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.

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A Chinese family with familial hemiplegic migraine type 2 due to a novel missense mutation in ATP1A2

Cephalalgia ◽

10.1177/0333102419847738 ◽

2019 ◽

Vol 39 (11) ◽

pp. 1382-1395

Author(s):

Wenjing Tang ◽

Meichen Zhang ◽

Enchao Qiu ◽

Shanshan Kong ◽

Yingji Li ◽

...

Keyword(s):

Missense Mutation ◽

Novel Mutation ◽

Clinical Manifestations ◽

Pathogenic Mutation ◽

Familial Hemiplegic Migraine ◽

Chinese Family ◽

Hemiplegic Migraine ◽

Pathogenic Potential ◽

The Family

Background ATP1A2 has been identified as the genetic cause of familial hemiplegic migraine type 2. Over 80 ATP1A2 mutations have been reported, but no data from Chinese family studies has been included. Here, we report the first familial hemiplegic migraine type 2 Chinese family with a novel missense mutation. Methods Clinical manifestations in the family were recorded. Blood samples from patients and the unaffected members were collected for whole-exome sequencing to identify the pathogenic mutation. Seven online softwares (SIFT, PolyPhen-2, PROVEAN, PANTHER, MutationTaster2, MutationAssessor and PMut) were used for predicting the pathogenic potential of the mutation. PredictProtein, Jpred 4 and PyMOL were used to analyze structural changes of the protein. The mutation function was further tested by Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay. Results All patients in the family had typical hemiplegic migraine attacks. Co-segregation of the mutation with the migraine phenotype in four generations, with 10 patients, was completed. The identified novel mutation, G762S in ATP1A2, exhibited the disease-causing feature by all the predictive softwares. The mutation impaired the local structure of the protein and decreased cell viability. Conclusion G762S in ATP1A2 is a novel pathogenic mutation identified in a Chinese family with familial hemiplegic migraine, which causes loss of function by changing the protein structure of the Na+/K+-ATPase α2 subunit.

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A novel missense mutation of CRYBB1 causes congenital cataract in a Chinese family

European Journal of Ophthalmology ◽

10.1177/1120672120914497 ◽

2020 ◽

pp. 112067212091449

Author(s):

Yanan Ji ◽

Xiangyu Zhao ◽

Juanmei Zhang ◽

Dan Zhang ◽

Chunliu Tian ◽

...

Keyword(s):

Missense Mutation ◽

Protein Function ◽

Congenital Cataract ◽

Family Members ◽

Causative Mutation ◽

Chinese Family ◽

Heterozygous Mutation ◽

Nuclear Cataract ◽

Mutation Site ◽

The Family

Objective of the study: To identify the pathogenic gene and mutation site of a Chinese family with congenital cataract. Methods: Eight family members and 100 controls were employed, and targeted exome sequencing was used to identify the genetically pathogenic factor of the proband. Results: Targeted next-generation sequencing identified a novel missense mutation c.209A>C (p.Q70P) of CRYBB1 gene in the family. Sanger sequencing results showed that this heterozygous mutation was a causative mutation, which was not found in unaffected family members and healthy controls. Bioinformatics predicts that the effect of this mutation on protein function is probably harmful. Conclusion: We demonstrate that c.209A>C of CRYBB1 gene is a pathogenic mutation in the family of congenital nuclear cataract in this study. This is the first report that this mutation leads to congenital nuclear cataract, which broadens the mutation spectrum of CRYBB1 gene in congenital nuclear cataract.

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A novel missense mutation of CRYBA1 in a northern Chinese family with inherited coronary cataract with blue punctate opacities

European Journal of Ophthalmology ◽

10.1177/11206721211008355 ◽

2021 ◽

pp. 112067212110083

Author(s):

Shu-Hua Ni ◽

Juan-Mei Zhang ◽

Jun Zhao

Keyword(s):

Missense Mutation ◽

High Throughput Sequencing ◽

Bioinformatics Analysis ◽

Genetic Defect ◽

Kinase Domain ◽

Chinese Family ◽

Heterozygous Mutation ◽

Scale Invariant ◽

The Family ◽

Northern Chinese

Purpose: To demonstrate the underlying genetic defect that contribute to inherited cataract in a northern Chinese pedigree. Methods: The study recruited a family pedigree with a diagnosis of bilateral coronary cataract with blue punctate opacities. Fourteen family members and 100 healthy volunteers were enrolled. DNA sample of the proband in this family were analyzed by high-throughput sequencing, which was then demonstrated by Sanger sequencing in the remained people in the family and 100 controls. The functional effect of mutant genes was investigated via bioinformatics analysis, including Polymorphism Phenotyping version2 (PolyPhen-2), Protein Variation Effect Analyzer (PROVEAN v1.1.3) Scale-Invariant Feature Transform (SIFT), and Mutation Taster. Results: In this three-generation family, a novel heterozygous mutation was found in the kinase domain of CRYBA1 gene (c.340C > T, p.R114C), which was only detected in patients in the family with inherited cataract and were not detected in the remained people in the family nor in normal people. The pathogenic effect of the mutation was verified via bioinformatics analysis. Conclusion: Our study presented the molecular experiments to confirm that a novel missense mutation of c.340 C > T located in exon 4 of CRYBA1 gene results in a bilateral coronary cataract with blue punctate opacities, which enriches the mutation spectrum of CRYBA1 gene in inherited cataract and deepens the understanding of the pathogenesis of inherited cataract.

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Dominant optic atrophy, sensorineural hearing loss, ptosis, and ophthalmoplegia: A syndrome caused by a missense mutation in OPA1

American Journal of Ophthalmology ◽

10.1016/j.ajo.2004.06.011 ◽

2004 ◽

Vol 138 (5) ◽

pp. 749-755 ◽

Cited By ~ 68

Author(s):

Marielle Payne ◽

Zhenglin Yang ◽

Bradley J. Katz ◽

Judith E.A. Warner ◽

Christopher J. Weight ◽

...

Keyword(s):

Hearing Loss ◽

Sensorineural Hearing Loss ◽

Missense Mutation ◽

Optic Atrophy ◽

Sensorineural Hearing ◽

Dominant Optic Atrophy

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Analysis of the JAK2 Gene cDNA Full-Length In One Chinese Familial Myeloproliferative Disorders

Blood ◽

10.1182/blood.v116.21.5056.5056 ◽

2010 ◽

Vol 116 (21) ◽

pp. 5056-5056

Author(s):

Ru Feng ◽

Lixia Hao ◽

Yongmin Zhang ◽

Yongqiang Wei ◽

Fen Huang ◽

...

Keyword(s):

Family Members ◽

Gene Mutations ◽

Myeloproliferative Disorders ◽

Full Length ◽

The Other ◽

Jak2v617f Mutation ◽

Chinese Family ◽

Heterozygous Mutation ◽

Homozygous Mutation ◽

The Family

Abstract Abstract 5056 Introduction: JAK2V617F point mutation have been confirmed to be one of the major molecular mechanism of BCR/ABL negative myeloproliferative disorders(MPD). Besides, some other gene mutations such as JAK2 exon12, MPL W515L/K, c-mpl and EPOR have extended the scope of the research in this field. Most of the MPD patients are sporadic and there are seldom reports in Chinese familial MPD. 2008 ASH metting we have reported in a Chinese family of MPD's findings, the two brothers in our hospital diagnosis for MPD (one is a PV, another is ET), then we investigated the 15 members of the family. We discovered that there were three male members carried the JAK2V617F mutation in this family, including the two MPD patients and their father, which affected in two generations. All the family members were confirmed as BCR/ABL, MPL W515L/K, c-mpl, and EPOR negative. Subsequently, in order to understand the existence of family members in addition to the gene JAK2 V617F mutation, the existence of JAK2 gene mutations in other parts of the? if other mutations in existence and the high incidence of family members of MPD? We focus on the cDNA full-length of JAK2 gene to provide some theory basis on the pathogenesis in MPD. Methods: A total of 15 family members were enrolled in our study, including 2 brothers of MPD patients (the older one was thrombocythemia (ET), and another is polycythemia vera (PV)) and the other members in the same family. The mRNA of mononuclear cells from peripheral blood sample was extracted according to the manufacturer's instruction (TAKARA). RT-PCR and DNA sequencing have been used to analyze the cDNA full-length of the JAK2 gene. Results: All of the samples can be analyzed for JAK2 cDNA full-length. 3 members carried the JAK2V617F mutation (1849G®T) in this family, including the two MPD patients and their father. And the older brother was homozygous mutation and the other two were heterozygous mutation. All of the 15 samples were JAK2 exon12 gene mutation negative. 2 persons who were the male ET patient's children had a heterozygous mutation (380G®A) in JAK2 exon 3, caused a glycine-to-asparticacid substitution at position 127. Besides, 13 persons had 489C®T mutation in exon 4 and 14 persons had 2490G→A mutation in exon 17 in this family, But they were both same-sense mutation. Conclusion: It is necessary to do routine analysis of blood and other related inspection for MPD patient's family members, so as to make diagnosis earlier. However, we are not sure that the sequencing results are unique to all the familial MPD and need to be confirmed by more cases. We still do not determine the current discovery point mutations have biological significance, still need to be further explored. Disclosures: No relevant conflicts of interest to declare.

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Identification of the FirstDe Novo UBIAD1Gene Mutation Associated with Schnyder Corneal Dystrophy

Journal of Ophthalmology ◽

10.1155/2016/1968493 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Benjamin R. Lin ◽

Ricardo F. Frausto ◽

Rosalind C. Vo ◽

Stephan Y. Chiu ◽

Judy L. Chen ◽

...

Keyword(s):

Family History ◽

Missense Mutation ◽

Protein Function ◽

De Novo ◽

Family Members ◽

Corneal Dystrophy ◽

Slit Lamp ◽

Slit Lamp Examination ◽

The Family ◽

Schnyder Corneal Dystrophy

Purpose.To report the identification of the firstde novo UBIAD1missense mutation in an individual with Schnyder corneal dystrophy (SCD).Methods.A slit lamp examination was performed on a 47-year-old woman without a family history of corneal disorders. The proband’s parents, two sisters, and son were also examined and genomic DNA from all six individuals was collected. The exons and exon-intron boundaries ofUBIAD1were screened using Sanger sequencing. Identified mutations were screened for in 200 control chromosomes.In silicoanalysis predicted the impact of identified mutations on protein function and structure.Results.Slit lamp examination of the proband revealed findings consistent with SCD. Corneas of the family members appeared unaffected. Screening ofUBIAD1in the proband identified a novel heterozygous c.308C>T mutation, predicted to encode the missense amino acid substitution p.(Thr103Ile). This mutation was not identified in any of the family members or in 200 control chromosomes and was predicted to be damaging to normal protein function and structure.Conclusions.We present a novel heterozygousde novomissense mutation inUBIAD1, p.(Thr103Ile), identified in a patient with classic clinical features of SCD. This highlights the value of genetic testing in clinical diagnostic settings, even in the absence of a positive family history.

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Different outcome of COVID-19 in members of a family

The Journal of Infection in Developing Countries ◽

10.3855/jidc.12792 ◽

2020 ◽

Vol 14 (05) ◽

pp. 447-449

Author(s):

Jin Sun ◽

Yan Jiang ◽

Wei Lin ◽

Wei-Hua Hu ◽

Yong Wang

Keyword(s):

Disease Progression ◽

Close Contact ◽

Family Members ◽

Clinical Manifestations ◽

Family Cluster ◽

The Family

We report a family cluster of cases of coronavirus disease 2019 (COVID-19), in which three members of the family were exposed to SARS-CoV-2 at the same time, but the disease manifested differently among the three family members. We describe the clinical manifestations, disease progression, and treatment of wife and husband. We also analyze the daughter who was in close contact with patients with COVID-19 but was not infected.

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

10.21203/rs.2.14948/v5 ◽

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.

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A Study on the Impact of Chinese Family Culture on Citizens' Voluntary Organ Donation

10.21203/rs.3.rs-35235/v1 ◽

2020 ◽

Author(s):

Aijing Luo ◽

Haiyan He ◽

Wenzhao Xie ◽

Zehua Xu ◽

Wei Ouyang ◽

...

Keyword(s):

Organ Donation ◽

Family Members ◽

Chinese Family ◽

Family Culture ◽

Willingness To Donate ◽

Culture Model ◽

The Family ◽

Culture Models ◽

Social And Cultural Factors ◽

The Impact

Abstract Objectives: Family members’ attitude is the key factor in organ donation. This study aimed to analyze the attitude and willingness of families towards organ donation and to explore the impact of Chinese family culture on voluntary organ donation.Methods: Taking the family as a unit, a total of 15 families (59 family members) were interviewed using the semi-structured interviews.Results: Among the 59 participants, 58 had heard of organ donation, 30 were unwilling to donate organs, 25 had an intention to donate, and 13 were very taboo about it. 29 weren’t giving consent for family members’ donation, only 8 supported families to sign up as donors. Particularly, 7 participants could donate their organs but wouldn’t donate organs of family members. The family culture models were divided into the patriarchal family culture model (4 families), independent family culture model (8 families), patriarchal subversion family culture model (3 families). Based on the influence of social and cultural factors (taking national policy as an example) on the willingness to donate organs of relatives, the family culture models were divided into the stubborn family culture model (3 families), swing family culture model(9 families), and selfless dedication family culture model(3 families). Conclusions: Organ donation is still a taboo topic in Chinese families. Although the patriarchal family cultural model is no longer dominant, the father's thoughts and views still play an essential role in the whole family. Most families belong to the swing family culture model, and the willingness to donate is greatly influenced by social and cultural factors.

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