A novel missense mutation p.S305R of EDA gene causes XLHED in a Chinese family

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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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 congenital Dysfibrinogenemia carries a heterozygous missense mutation in FGA: Concerning the genetic abnormality and clinical treatment

Pakistan Journal of Medical Sciences ◽

10.12669/pjms.334.12828 ◽

2017 ◽

Vol 33 (4) ◽

Cited By ~ 2

Author(s):

Jihao Zhou ◽

Peng Zhu ◽

Xinyou Zhang

Keyword(s):

Missense Mutation ◽

Clinical Treatment ◽

Chinese Family ◽

Genetic Abnormality ◽

Heterozygous Missense Mutation

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Familial amyloid polyneuropathy with chronic paroxysmal dry cough in Mainland China: A Chinese family with a proven heterozygous missense mutation c.349G>T in the transthyretin gene

Journal of Clinical Neuroscience ◽

10.1016/j.jocn.2018.10.040 ◽

2019 ◽

Vol 60 ◽

pp. 164-166 ◽

Cited By ~ 3

Author(s):

Zhenhua Yuan ◽

Lina Guo ◽

Xixi Liu ◽

Xuewen Xiao ◽

Bin Jiao ◽

...

Keyword(s):

Missense Mutation ◽

Mainland China ◽

Familial Amyloid Polyneuropathy ◽

Chinese Family ◽

Heterozygous Missense Mutation ◽

Amyloid Polyneuropathy

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A novel c.287G>T NDP missense mutation in a Chinese family with Norrie disease

Ophthalmic Genetics ◽

10.1080/13816810.2020.1759106 ◽

2020 ◽

Vol 41 (4) ◽

pp. 338-340

Author(s):

Meina Lin ◽

Yongping Lu ◽

Yu Sui ◽

Xiang Ni ◽

Huan Li ◽

...

Keyword(s):

Missense Mutation ◽

Chinese Family ◽

Norrie Disease

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Macular corneal dystrophy related to novel mutations of CHST6 in a Chinese family and clinical observation after penetrating keratoplasty

BMC Medical Genomics ◽

10.1186/s12920-021-01095-7 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Dewei Li ◽

Le Tian ◽

Xiaochuan Wang ◽

Min Chen

Keyword(s):

Missense Mutation ◽

Penetrating Keratoplasty ◽

Vision Loss ◽

Corneal Dystrophy ◽

Postoperative Recurrence ◽

Deletion Mutation ◽

Chinese Family ◽

Colloidal Iron ◽

Macular Corneal Dystrophy

Abstract Background Macular corneal dystrophy (MCD) is a rare corneal stromal dystrophy with bilateral progressive vision loss. The pathogenic gene of MCD is carbohydrate sulfotransferase 6 (CHST6). Herein, we report a novel missense mutation and a rare exon deletion mutation in the CHST6 gene in a Chinese family with MCD. Methods Genomic DNA was extracted from the peripheral blood, and next generation sequencing was used to analyse the gene sequence. The pathogenic mutations were identified in all affected family members. The proband successively received binocular penetrating keratoplasty (PKP), and the corneas were examined by histopathology and colloidal iron staining to prove the diagnosis. A long-term follow-up was made to observe the changes after PKP. Results Genetic analysis demonstrated hemizygous mutations in the proband, including a novel c.520A>C (p.K174Q) missense mutation and a rarely reported exon 3 deletion mutation, which were co-segregated with the MCD phenotypes in the pedigree. The positive colloidal iron staining confirmed the diagnosis of MCD in the proband. However, the clinical phenotype and pathological manifestation of both eyes were different from each other because of complicated keratitis in the left eye. During the nine years of follow-up, visual acuity was improved significantly, and the cornea was transparent without rejection and postoperative recurrence in both eyes. Conclusions The novel hemizygous mutations were thought to contribute to the loss of CHST6 function, which induced typical clinical and pathological features of MCD. PKP was an effective treatment for MCD.

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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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