Identification of pathogenic mutations in 6 Chinese families with multiple exostoses by whole-exome sequencing and multiplex ligation-dependent probe amplification

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.

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Whole Exome Sequencing of Six Chinese Families With Hereditary Non-Syndromic Hearing Loss: A Genetic Etiology Study

10.21203/rs.3.rs-132767/v1 ◽

2020 ◽

Author(s):

Pengfei Liang ◽

Fengping Chen ◽

Shujuan Wang ◽

Qiong Li ◽

Wei Li ◽

...

Keyword(s):

Hearing Loss ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Sanger Sequencing ◽

Large Scale ◽

Autosomal Recessive ◽

Autosomal Recessive Inheritance ◽

Chinese Families ◽

Whole Exome ◽

Syndromic Hearing Loss

Abstract Background: Hereditary non-syndromic hearing loss (NSHL) has a high genetic heterogeneity with >152 genes identified as associated molecular causes. The present study aimed to detect the possible damaging variants of the deaf probands from six unrelated Chinese families.Methods: After excluding the mutations in the most common genes, GJB2 and SLC26A4, 12 probands with prelingual deafness and autosomal recessive inheritance were evaluated by whole-exome sequencing (WES). All the candidate variants were verified by Sanger sequencing in all patients and their parents.Results: Biallelic mutations were identified in all deaf patients. Among these six families, 10 potentially causative mutations, including 3 reported and 7 novel mutations, in 3 different deafness-associated autosomal recessive (DFNB) genes (MYO15A, COL11A2, and CDH23) were identified. The mutations in MYO15A were frequent with 7/10 candidate variants. Sanger sequencing confirmed that these mutations segregated with the hearing loss of each family.Conclusions: Next-generation sequencing (NGS) approach becomes more cost-effective and efficient when analyzing large-scale genes compared to the conventional polymerase chain reaction-based Sanger sequencing, which is often used to screen common deafness-related genes. The current findings further extend the mutation spectrum of hearing loss in the Chinese population, which has a positive significance for genetic counseling.

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Identification of two novel mutations in three Chinese families with Kallmann syndrome using whole exome sequencing

Andrologia ◽

10.1111/and.13594 ◽

2020 ◽

Vol 52 (7) ◽

Cited By ~ 1

Author(s):

Qin Zhang ◽

Hong‐hui He ◽

Muhammad Usman Janjua ◽

Fang Wang ◽

You‐bo Yang ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Kallmann Syndrome ◽

Novel Mutations ◽

Chinese Families ◽

Whole Exome

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Whole exome sequencing and methylation‑specific multiplex ligation‑dependent probe amplification applied to identify Angelman syndrome due to paternal uniparental disomy in two unrelated patients

Molecular Medicine Reports ◽

10.3892/mmr.2019.10339 ◽

2019 ◽

Author(s):

Haibei Li ◽

Haiqi Yang ◽

Nan Lv ◽

Caiyun Ma ◽

Jingjie Li ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Angelman Syndrome ◽

Uniparental Disomy ◽

Whole Exome ◽

Paternal Uniparental Disomy ◽

Dependent Probe

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Whole-Exome Sequencing Identifies Two Novel TTN Mutations in Chinese Families with Dilated Cardiomyopathy

Cardiology ◽

10.1159/000447422 ◽

2016 ◽

Vol 136 (1) ◽

pp. 10-14 ◽

Cited By ~ 5

Author(s):

Ji-Shi Liu ◽

Liang-Liang Fan ◽

Hao Zhang ◽

Xiaoxian Liu ◽

Hao Huang ◽

...

Keyword(s):

Dilated Cardiomyopathy ◽

Exome Sequencing ◽

Missense Mutation ◽

Whole Exome Sequencing ◽

Nonsense Mutation ◽

Novel Mutations ◽

Chinese Families ◽

Structure Changes ◽

Whole Exome ◽

Gene Filtering

Objectives: Dilated cardiomyopathy (DCM) is a leading cause of sudden cardiac death. So far, only 127 mutations of Titin(TTN) have been reported in patients with different phenotypes such as isolated cardiomyopathies, purely skeletal muscle phenotypes or complex overlapping disorders of muscles. Methods: We applied whole-exome sequencing (WES) to investigate cardiomyopathy patients and a cardiomyopathy-related gene-filtering strategy was used to analyze the disease-causing mutations. Sanger sequencing was applied to confirm the mutation cosegregation in the affected families. Results: A nonsense mutation (c.12325C>T/p.R4109X) and a missense mutation (c.17755G>C/p.G5919R) of TTN were identified in 2 Chinese DCM families, respectively. Both mutations were cosegregated in all affected members of both families. The nonsense mutation is predicted to result in a truncated TTN protein and the missense mutation leads to a substitution of glycine by arginine. Both variants may cause the structure changes of titin protein. Conclusions: We employed WES to detect the mutations of DCM patients and identified 2 novel mutations. Our study expands the spectrum of TTN mutations and offers accurate genetic testing information for DCM patients who are still clinically negative.

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