scholarly journals Whole-exome Sequencing Reveals the Etiology of the Rare Primary Hepatic Mucoepidermoid Carcinoma

2020 ◽  
Author(s):  
Ping Hou ◽  
Xiaoyan Su ◽  
Wei Cao ◽  
Liping Xu ◽  
Rongguiyi Zhang ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Mucoepidermoid Carcinoma ◽  
Sanger Sequencing ◽  
Susceptibility Genes ◽  
Fanconi's Anemia ◽  
Whole Exome ◽  
Fanconi’S Anemia ◽  
Public Data ◽  
Molecular Etiology

Abstract Background Primary hepatic mucoepidermoid carcinoma (HMEC)is extremely rare and the molecular etiology is still unknown.Recently, The CRTC1-MAML2 fusion gene was detected in a primary HMEC which is often associated with MEC of salivary gland in the literature. Methods a 64-year-old male was diagnosed with HMEC based on malignant squamous cells and mucus-secreting cells in immunohistochemical examination. Whole-exome sequencing(WES) and sanger sequencing were used to reveal the molecular characteristics of HMEC,and analysis with public datas among hepatocellular carcinoma, cholangiocarcinoma and salivary MEC. Meanwhile, The susceptibility genes were identified in pedigree investigation.Result Significant somatic mutations in GNAS,KMT2C,ELF3 genes were identified in primary HMEC by WES and sanger sequencing. Meanwhile, through public data analysis, somtatic GNAS gene alterd in 2.1% hepatobiliary tumors, and typically GNAS occur at exon 8, in which Arg201 is converted to either a cysteine (R201C) or a histidine (R201H) related with cholangiocarcinoma associated with parasite infection .Furthermore, heterozygous germline mutations of FANCA, FANCI, FANCJ/BRIP1 and FAN1 genes were also identified. Pedigree investigation verified that mutation of susceptibility genes of Fanconi's anemia were present in the pedigree.Conclusions It was the first time to demonstrate the molecular etiology of the rare HMEC associated with germline Fanconi’s anemia mutations and somatic GNAS R201H mutation.

scholarly journals Whole-exome sequencing reveals the etiology of the rare primary hepatic mucoepidermoid carcinoma

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Ping Hou ◽  
Xiaoyan Su ◽  
Wei Cao ◽  
Liping Xu ◽  
Rongguiyi Zhang ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Mucoepidermoid Carcinoma ◽  
Fusion Gene ◽  
Susceptibility Genes ◽  
Fanconi's Anemia ◽  
Whole Exome ◽  
Fanconi’S Anemia ◽  
Public Data ◽  
Molecular Etiology

Abstract Background Primary hepatic mucoepidermoid carcinoma (HMEC) is extremely rare and the molecular etiology is still unknown. The CRTC1-MAML2 fusion gene was previously detected in a primary HMEC, which is often associated with MEC of salivary gland in the literature. Methods A 64-year-old male was diagnosed with HMEC based on malignant squamous cells and mucus-secreting cells in immunohistochemical examination. Fluorescence in situ hybridization (FISH) was used to detect the CRTC1-MAML2 fusion gene in HMEC. Whole-exome sequencing and Sanger sequencing were used to reveal the molecular characteristics of HMEC and analysis was performed with public data. Pedigree investigation was performed to identify susceptibility genes. Results Hematoxylin–eosin staining and immunohistochemistry revealed that the tumor cells were composed of malignant epidermoid malignant cells and mucous cells, indicating a diagnosis of HMEC. The CRTC1-MAML2 fusion gene was not detected in the primary HMEC, and somatic mutations in GNAS, KMT2C and ELF3 genes were identified by sequencing. Analyses of public data revealed somatic GNAS alterations in 2.1% hepatobiliary tumors and relation with parasite infection. Heterozygous germline mutations of FANCA, FANCI, FANCJ/BRIP1 and FAN1 genes were also identified. Pedigree investigation verified that mutation of Fanconi’s anemia susceptibility genes were present in the pedigree. Conclusions Here we provide the first evidence of the molecular etiology of a rare HMEC associated with germline Fanconi’s anemia gene mutations and somatic GNAS R201H mutation.

scholarly journals Screening of Graves' Disease Susceptibility Genes by Whole Exome Sequencing in a Three-generation Family

2020 ◽  
Author(s):  
Zhuoqing Hu ◽  
Wei Li ◽  
Miaosheng Li ◽  
Hao Wei ◽  
Zhihui Hu ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Familial Aggregation ◽  
Susceptibility Genes ◽  
Graves Disease ◽  
Chinese Han ◽  
Whole Exome ◽  
Generation Family ◽  
Protein Functions

Abstract Background: Graves’ disease(GD) has a tendency for familial aggregation, but it is uncommon to occur in more than two generations. Little is known about susceptibility genes for GD in the three-generation family.Methods: DNA were extracted from three-generation familial GD patient with a strong genetic background in a Chinese Han population. We utilize the Whole Exome Sequencing(WES) to screen and the Sanger sequencing confirmed potential disease-causing genes.Results:In this case study, there are five patients with Graves’ disease(GD) from a three-generation family. We firstly revealed the SNVs of MAP7D2(c. 452C>T: p. A151V), SLC1A7(c. 1204C>T: p. R402C), TRAF3IP3(c. 209A>T: p. N70I), PTPRB(c. 3472A>G: p. S1158G), PIK3R3(c. 121C>T: p. P41S), DISC1(c. 1591G>C: p. G531R) were associated with the familial GD. The Sanger sequencing confirmed these variations and more importantly is that the PolyPhen-2 score showed that the variants in TRAF3IP3, PTPRB, PIK3R3 are more likely to change protein functions.Conclusion: The MAP7D2, SLC1A7, TRAF3IP3, PTPRB, PIK3R3, DISC1 may be the candidate susceptibility genes for familial GD from a three generations family.

scholarly journals Screening of Graves' Disease Susceptibility Genes by Whole Exome Sequencing in a Three-generation Family

2021 ◽  
Author(s):  
Zhuoqing Hu ◽  
Wei Li ◽  
Miaosheng Li ◽  
Hao Wei ◽  
Zhihui Hu ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Familial Aggregation ◽  
Susceptibility Genes ◽  
Graves Disease ◽  
Chinese Han ◽  
Whole Exome ◽  
Generation Family ◽  
Protein Functions

Abstract Background Graves’ disease(GD) has a tendency for familial aggregation, but it is uncommon to occur in more than two generations. However, little is known about susceptibility genes for GD in the three-generation family. Methods DNA were extracted from three-generation familial GD patient with a strong genetic background in a Chinese Han population. The Whole Exome Sequencing (WES) was utilized to screen the genome for SNVs associated with GD and the Sanger Sequencing was used to confirm the potential disease-causing genes. Results In the case study, there were five patients with Graves’ disease(GD) from a three-generation family. The SNVs of MAP7D2(c. 452C > T: p. A151V), SLC1A7(c. 1204C > T: p. R402C), TRAF3IP3(c. 209A > T: p. N70I), PTPRB(c. 3472A > G: p. S1158G), PIK3R3(c. 121C > T: p. P41S), DISC1(c. 1591G > C: p. G531R) were found to be associated with the familial GD and the Sanger sequencing had confirmed these variations. Furthermore, PolyPhen-2 score showed that the variants in TRAF3IP3, PTPRB, PIK3R3 are more likely to change protein functions. Conclusion The MAP7D2, SLC1A7, TRAF3IP3, PTPRB, PIK3R3, DISC1 may be the candidate susceptibility genes for familial GD from a three generations family.

scholarly journals Screening of Graves' Disease Susceptibility Genes by Whole Exome Sequencing in a Three-generation Family

2020 ◽  
Author(s):  
Zhuoqing Hu ◽  
Wei Li ◽  
Miaosheng Li ◽  
Hao Wei ◽  
Zhihui Hu ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Familial Aggregation ◽  
Susceptibility Genes ◽  
Graves Disease ◽  
Chinese Han ◽  
Whole Exome ◽  
Generation Family ◽  
Protein Functions

Abstract Background: Graves’ disease(GD) has a tendency for familial aggregation, but it is uncommon to occur in more than two generations. However, little is known about susceptibility genes for GD in the three-generation family.Methods: DNA were extracted from three-generation familial GD patient with a strong genetic background in a Chinese Han population. The Whole Exome Sequencing (WES) was utilized to screen the genome for SNVs associated with GD and the Sanger Sequencing was used to confirm the potential disease-causing genes.Results: In the case study, there were five patients with Graves’ disease(GD) from a three-generation family. The SNVs of MAP7D2(c. 452C>T: p. A151V), SLC1A7(c. 1204C>T: p. R402C), TRAF3IP3(c. 209A>T: p. N70I), PTPRB(c. 3472A>G: p. S1158G), PIK3R3(c. 121C>T: p. P41S), DISC1(c. 1591G>C: p. G531R) were found to be associated with the familial GD and the Sanger sequencing had confirmed these variations. Furthermore, PolyPhen-2 score showed that the variants in TRAF3IP3, PTPRB, PIK3R3 are more likely to change protein functions.Conclusion: The MAP7D2, SLC1A7, TRAF3IP3, PTPRB, PIK3R3, DISC1 may be the candidate susceptibility genes for familial GD from a three generations family.

scholarly journals Screening of Graves' disease susceptibility genes by whole exome sequencing in a three-generation family

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Zhuoqing Hu ◽  
Wei Li ◽  
Miaosheng Li ◽  
Hao Wei ◽  
Zhihui Hu ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Familial Aggregation ◽  
Susceptibility Genes ◽  
Graves Disease ◽  
Chinese Han ◽  
Whole Exome ◽  
Generation Family ◽  
Protein Functions

Abstract Background Graves’ disease(GD) has a tendency for familial aggregation, but it is uncommon to occur in more than two generations. However, little is known about susceptibility genes for GD in the three-generation family. Methods DNA were extracted from three-generation familial GD patient with a strong genetic background in a Chinese Han population. The Whole Exome Sequencing (WES) was utilized to screen the genome for SNVs associated with GD and the Sanger Sequencing was used to confirm the potential disease-causing genes. Results In the case study, there were five patients with Graves’ disease(GD) from a three-generation family. The SNVs of MAP7D2(c. 452C > T: p. A151V), SLC1A7(c. 1204C > T: p. R402C), TRAF3IP3(c. 209A > T: p. N70I), PTPRB(c. 3472A > G: p. S1158G), PIK3R3(c. 121C > T: p. P41S), DISC1(c. 1591G > C: p. G531R) were found to be associated with the familial GD and the Sanger sequencing had confirmed these variations. Furthermore, PolyPhen-2 score showed that the variants in TRAF3IP3, PTPRB, PIK3R3 are more likely to change protein functions. Conclusion The MAP7D2, SLC1A7, TRAF3IP3, PTPRB, PIK3R3, DISC1 may be the candidate susceptibility genes for familial GD from a three generations family.

scholarly journals NAPG mutation in family members with hereditary hemorrhagic telangiectasia in China

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yu Xu ◽  
Yong-Biao Zhang ◽  
Li-Jun Liang ◽  
Jia-Li Tian ◽  
Jin-Ming Lin ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Hereditary Hemorrhagic Telangiectasia ◽  
Sanger Sequencing ◽  
Conformational Stability ◽  
Sequencing Analysis ◽  
Large Pedigree ◽  
Whole Exome ◽  
Variant Filtering ◽  
Genetic Contributions

Abstract Background Hereditary hemorrhagic telangiectasia (HHT) is a disease characterized by arteriovenous malformations in the skin and mucous membranes. We enrolled a large pedigree comprising 32 living members, and screened for mutations responsible for HHT. Methods We performed whole-exome sequencing to identify novel mutations in the pedigree after excluding three previously reported HHT-related genes using Sanger sequencing. We then performed in silico functional analysis of candidate mutations that were obtained using a variant filtering strategy to identify mutations responsible for HHT. Results After screening the HHT-related genes, activin A receptor-like type 1 (ACVRL1), endoglin (ENG), and SMAD family member 4 (SMAD4), we did not detect any co-segregated mutations in this pedigree. Whole-exome sequencing analysis of 7 members and Sanger sequencing analysis of 16 additional members identified a mutation (c.784A > G) in the NSF attachment protein gamma (NAPG) gene that co-segregated with the disease. Functional prediction showed that the mutation was deleterious and might change the conformational stability of the NAPG protein. Conclusions NAPG c.784A > G may potentially lead to HHT. These results expand the current understanding of the genetic contributions to HHT pathogenesis.

scholarly journals A homozygous mutation of GNRHR in a familial case diagnosed with polycystic ovary syndrome

2017 ◽  
Vol 176 (5) ◽  
pp. K9-K14 ◽  
Author(s):  
Sandrine Caburet ◽  
Ronit Beck Fruchter ◽  
Bérangère Legois ◽  
Marc Fellous ◽  
Stavit Shalev ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Polycystic Ovary ◽  
Missense Variant ◽  
Genetic Alterations ◽  
Homozygous Mutation ◽  
Gonadotropin Secretion ◽  
Whole Exome ◽  
A Genome

Context PCOS is a heterogeneous condition characterized by hyperandrogenism and chronic anovulation and affects about 10% of women. Its etiology is poorly known, but a dysregulation of gonadotropin secretion is one of its hallmarks. Objective As the etiology of PCOS is unclear, we have performed a genome-wide analysis of a consanguineous family with three sisters diagnosed with PCOS. Methods Whole-exome sequencing and Sanger sequencing confirmation. Results Whole-exome sequencing allowed the detection of the missense variant rs104893836 located in the first coding exon of the GNRHR gene and leading to the p.Gln106Arg (p.Q106R) substitution. Sanger sequencing of all available individuals of the family confirmed that the variant was homozygous in the three affected sisters and heterozygous in both parents. Conclusions This is the first description of a GNRHR gene mutation in patients diagnosed with PCOS. Although we do not exclude a possible interaction of the identified variant with the genetic background and/or the environment, our result suggests that genetic alterations in the hypothalamo–pituitary axis may play role in the pathogenesis of PCOS.

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

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.

scholarly journals The Profile of Genetic Mutations in Papillary Thyroid Cancer Detected by Whole Exome Sequencing

2018 ◽  
Vol 50 (1) ◽  
pp. 169-178 ◽  
Author(s):  
Yi Fang ◽  
Xiao Ma ◽  
Jing Zeng ◽  
Yanwen Jin ◽  
Yong Hu ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Exome Sequencing ◽  
Papillary Thyroid Cancer ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Signal Pathways ◽  
Papillary Thyroid ◽  
Driver Genes ◽  
Mutational Status ◽  
Whole Exome

Background/Aims: The purpose of the study was to investigate the altered driver genes and signal pathways during progression of papillary thyroid cancer (PTC) via next-generation sequencing technology. Methods: The DNA samples for whole exome sequencing (WES) analyses were extracted from 11 PTC tissues and adjacent normal tissues samples. Direct Sanger sequencing was applied to validate the identified mutations. Results: Among the 11 pairs of tissues specimens, 299 single nucleotide variants (SNVs) in 75 genes were identified. The most common pattern of base pair substitutions was T:A>C:G (49.83%), followed by C:G>T:A (18.06%) and C:G>G:C (15.05%). The altered genes were mainly implicated in MAPK (mitogen-activated protein kinase), PPAR (peroxisome proliferator-activated receptors), and p53 signaling pathways. In addition, 12 novel identified driver genes were validated by Sanger sequencing. The mutations of FAM133A, DPCR1, JAK1, C10orf10, EPB41L3, GPRASP1 and IWS1 exhibited in multiple PTC cases. Furthermore, the PTC cases exhibited individual mutational signature, even the same gene might present different mutational status in different cases. Conclusion: Multiple PTC-related somatic mutations and signal pathways are identified via WES and Sanger sequencing methods. The novel identified mutations in genes such as FAM133A, DPCR1, and JAK1 may be potential therapeutic targets for PTC patients.

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