Whole-exome sequencing identified a novel mutation of SLC20A2 (c.C1849T) in a Chinese family with hereditary multiple exostoses

2020 ◽  
Author(s):  
YiQiang Li ◽  
XueMei Lin ◽  
MingWei Zhu ◽  
FuXing Xun ◽  
JingChun Li ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Novel Mutation ◽  
Chinese Family ◽  
Bioinformatics Pipeline ◽  
Hereditary Multiple Exostoses ◽  
Whole Exome ◽  
Multiple Exostoses ◽  
Proliferation And Differentiation ◽  
Filtering Procedure

Abstract Background: Although the main causative genes for hereditary multiple exostoses (HME) are EXT-1 and EXT-2, there are still many HME patients without EXT-1 and EXT-2 mutations. This study aimed to identify novel candidate genes for the development of HME in patients without EXT-1 and EXT-2 mutations.Methods: Whole-exome sequencing was performed in a typical Chinese HME family without EXT-1 and EXT-2 mutations, followed by a combined bioinformatics pipeline including annotation and filtering process to identify candidate variants. Candidate variants were then validated by Sanger sequencing.Results: A total of 1830 original variants were revealed to be heterozygous mutations in the three patients suffering from HME that were not present in the healthy controls. Two mutations (c.C1849T in SLC20A2 and c.G506A in LETM1) were identified as a possible causative variant for HME through a bioinformatics filtering procedure and harmful prediction. Sanger sequencing results confirmed these two mutations in all patients with HME. A mutation in SLC20A2 (c.C1849T) led to a change in amino acid (p.R617C), which may be involved in the development of HME by inducing metabolic disorders of phosphate and abnormal proliferation and differentiation in chondrocytes.Conclusions: The present study revealed two mutations [SLC20A2 (c.C1849T) and LETM1 (c.G506A) in a Chinese HME family. The mutation in SLC20A2 (c.C1849T) is more likely to be involved in the development of HME.

scholarly journals Identification of a Novel EXT Mutation in A Kindred With Hereditary Multiple Exostoses Using Whole-Exome Sequencing and Overview of Mutation Spectrum

2021 ◽  
Author(s):  
yanhan deng ◽  
yujian liu ◽  
wei tu ◽  
liu yang
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Mutation Spectrum ◽  
Loss Of Function ◽  
Site Mutation ◽  
Hereditary Multiple Exostoses ◽  
Multiple Osteochondromas ◽  
Online Databases ◽  
Whole Exome ◽  
Multiple Exostoses

Abstract Background: Hereditary Multiple Osteochondromas(HMO) is a rare genetic musculoskeletal disorder characterized by multiple osteochondromas that form near to the growth plates of many bones. Loss-of-function mutations in EXT1 or EXT2 that encode glycosyltrasferases are the causal mutations for most HMO patients.Methods: After collecting the family history and clinical information, we used Whole-Exome Sequencing to find the pathogenic mutations in one Chinese Hereditary Multiple Exostoses pedigree. Sanger sequencing and relevant online databases were used to validate the screened variants. Lollipop plots were drew to map the reported mutations from online databases (Multiple Osteochondroma Mutation Database and clinvar)on a linear protein domains by MutationMapper.Results: A novel heterozygous splicing-site mutation in gene EXT1 (NM_000127:exon5:c.1417+1G>C，chr8:118834703) was found in this pedigree and mutation spectrum of genes EXT1 and EXT2 were demonstrated.Conclusions: Our results help this pedigree to identify the pathogenic variant and guide the prenatal diagnosis, also expand the mutation spectrum in Hereditary Multiple Osteochondromas.

scholarly journals Identification of a novel mutation in a Chinese family with Nance-Horan syndrome by whole exome sequencing

2014 ◽  
Vol 15 (8) ◽  
pp. 727-734 ◽  
Author(s):  
Nan Hong ◽  
Yan-hua Chen ◽  
Chen Xie ◽  
Bai-sheng Xu ◽  
Hui Huang ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Novel Mutation ◽  
Chinese Family ◽  
Whole Exome

scholarly journals Whole-Exome Sequencing Identifies a Novel TRPM4 Mutation in a Chinese Family with Atrioventricular Block

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Yi Dong ◽  
Ran Du ◽  
Liang-liang Fan ◽  
Jie-yuan Jin ◽  
Hao Huang ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Atrioventricular Block ◽  
Transient Receptor Potential ◽  
Novel Mutation ◽  
Receptor Potential ◽  
Cardiac Conduction ◽  
Chinese Family ◽  
Transient Receptor Potential Melastatin ◽  
Whole Exome

Atrioventricular block (AVB) is a leading cause of sudden cardiac death, and most of AVB cases are presented as autosomal dominant. The electrocardiogram of AVB patients presents an abnormal progressive cardiac conduction disorder between atria and ventricles. Transient receptor potential melastatin 4 (TRPM4) is a nonselective Ca2+-activated cation channel gene defined as a novel disease-causing gene of AVB. So far, 47 mutations of TRPM4 have been recorded in Human Gene Mutation Database. The aim of this study was to explore the relationship between TRPM4 mutation and pathogenesis of AVB. We investigated a Chinese family with AVB by whole-exome sequencing. An arrhythmia-related gene filtering strategy was used to analyze the disease-causing mutations. Three different bioinformatics programs were used to predict the effects of the mutation result. A novel mutation of TRPM4 was identified (c.2455C>T/p.R819C) and cosegregated in the affected family members. The three bioinformatics programs predicted that the novel mutation may lead to damage. Our study will contribute to expand the spectrum of TRPM4 mutations and supply accurate genetic testing information for further research and the clinical therapy of AVB.

scholarly journals A novel SPAST gene mutation identified in a Chinese family with hereditary spastic paraplegia

2020 ◽  
Author(s):  
Weiwei Yu ◽  
Haiqiang Jin ◽  
Jianwen Deng ◽  
Ding Nan ◽  
Yining Huang
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Hereditary Spastic Paraplegia ◽  
Dna Isolation ◽  
Tertiary Structure ◽  
Novel Mutation ◽  
Chinese Family ◽  
Spastic Paraplegia ◽  
Whole Exome ◽  
And Function

Abstract Background: Hereditary spastic paraplegia is a heterogeneous group of clinically and genetically neurodegenerative diseases characterized by progressive gait disorder. Hereditary spastic paraplegia can be inherited in various ways, and all modes of inheritance are associated with multiple genes or loci. At present, more than 76 disease-causing loci have been identified in hereditary spastic paraplegia patients. Here, we report a novel mutation in SPAST gene associated with hereditary spastic paraplegia in a Chinese family, further enriching the hereditary spastic paraplegia spectrum. Methods: Whole genomic DNA was extracted from peripheral blood of the 15 subjects from a Chinese family using DNA Isolation Kit. The Whole Exome Sequencing of the proband was analyzed and the result was identified in the rest individuals. RaptorX prediction tool and Protein Variation Effect Analyzer were used to predict the effects of the mutation on protein tertiary structure and function.Results: Spastic paraplegia has been inherited across at least four generations in this family, during which only four HSP patients were alive. The results obtained by analyzing the Whole Exome Sequencing of the proband exhibited a novel disease-associated in-frame deletion in the SPAST gene, and the this mutation also existed in the rest three HSP patients in this family. This in-frame deletion consists of three nucleotides deletion (c.1710_1712delGAA) within the exon 16, resulting in lysine deficiency at the position 570 of the protein (p.K570del). This novel mutation was also predicted to result in the synthesis of misfolded SPAST protein and have the deleterious effect on the function of SPAST protein.Conclusion: In this case, we reported a novel mutation in the known SPAST gene that segregated with HSP disease, which can be inherited in each generation. Simultaneously, this novel discovery significantly enriches the mutation spectrum, which provides an opportunity for further investigation of genetic pathogenesis of HSP.

Whole Exome Sequencing Identifies a Novel Mutation of TPK1 in a Chinese Family with Recurrent Ataxia

2020 ◽  
Vol 70 (8) ◽  
pp. 1237-1243
Author(s):  
Bizhen Zhu ◽  
Jinzhun Wu ◽  
Guobing Chen ◽  
Ling Chen ◽  
Yonghua Yao
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Novel Mutation ◽  
Chinese Family ◽  
Whole Exome
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