Identification of sequence variants associated with severe microtia-astresia by targeted sequencing.

Abstract:

BACKGROUND:Microtia-atresia is characterized by abnormalities of the auricle (microtia) and aplasia or hypoplasia of the external auditory canal, often associated with middle ear abnormalities. To date, no causal genetic mutations or genes have been identified in microtia-atresia patients. METHODS:We designed a panel of 131 genes associated with external/middle or inner ear deformity. Targeted genomic capturing combined with next-generation sequencing (NGS) was utilized to screen for mutations in 40 severe microtia-atresia patients. Mutations detected by NGS were filtered and validated. And then mutations were divided into three categories-rare or novel variants, low-frequency variants and common variants-based on their frequency in the public database. The rare or novel mutations were prioritized by pathogenicity analysis. For the low-frequency variants and common variants, we used association studies to explore risk factors of severe microtia-atresia. RESULTS:Sixty-five rare heterozygous mutations of 42 genes were identified in 27 (67.5%) severe microtia-atresia patients. Association studies to determine genes that were potentially pathogenic found that PLEC, USH2A, FREM2, DCHS1, GLI3, POMT1 and GBA genes were significantly associated with severe microtia-atresia. Of these, DCHS1 was strongly suggested to cause severe microtia-atresia as it was identified by both low-frequency and common variants association studies. A rare mutation (c.481C > T, p.R161C) in DCHS1 identified in one individual may be deleterious and may cause severe microtia-atresia. CONCLUSION:We identified several genes that were significantly associated with severe microtia-atresia. The findings provide new insights into genetic background of external ear deformities.

journal_name

BMC Med Genomics

journal_title

BMC medical genomics

authors

Wang P,Wang Y,Fan X,Liu Y,Fan Y,Liu T,Chen C,Zhang S,Chen X

doi

10.1186/s12920-019-0475-x

subject

Has Abstract

pub_date

2019-01-28 00:00:00

pages

28

issue

1

issn

1755-8794

pii

10.1186/s12920-019-0475-x

journal_volume

12

pub_type

杂志文章
  • Mosaic chromosome 18 anomaly delineated in a child with dysmorphism using a three-pronged cytogenetic techniques approach: a case report.

    abstract:BACKGROUND:A plethora of cases are reported in the literature with iso- and ring-chromosome 18. However, co-occurrence of these two abnormalities in an individual along with a third cell line and absence of numerical anomaly is extremely rare. CASE PRESENTATION:A 7-year-old female was referred for diagnosis due to gro...

    journal_title:BMC medical genomics

    pub_type: 杂志文章

    doi:10.1186/s12920-020-00796-9

    authors: Sheth H,Trivedi S,Liehr T,Patel K,Jain D,Sheth J,Sheth F

    更新日期:2020-09-24 00:00:00

  • Derivation of a bronchial genomic classifier for lung cancer in a prospective study of patients undergoing diagnostic bronchoscopy.

    abstract:BACKGROUND:The gene expression profile of cytologically-normal bronchial airway epithelial cells has previously been shown to be altered in patients with lung cancer. Although bronchoscopy is often used for the diagnosis of lung cancer, its sensitivity is imperfect, especially for small and peripheral suspicious lesion...

    journal_title:BMC medical genomics

    pub_type: 杂志文章,多中心研究

    doi:10.1186/s12920-015-0091-3

    authors: Whitney DH,Elashoff MR,Porta-Smith K,Gower AC,Vachani A,Ferguson JS,Silvestri GA,Brody JS,Lenburg ME,Spira A

    更新日期:2015-05-06 00:00:00

  • Small RNAs in metastatic and non-metastatic oral squamous cell carcinoma.

    abstract:BACKGROUND:Small non-coding regulatory RNAs control cellular functions at the transcriptional and post-transcriptional levels. Oral squamous cell carcinoma is among the leading cancers in the world and the presence of cervical lymph node metastases is currently its strongest prognostic factor. In this work we aimed at ...

    journal_title:BMC medical genomics

    pub_type: 杂志文章

    doi:10.1186/s12920-015-0102-4

    authors: Severino P,Oliveira LS,Andreghetto FM,Torres N,Curioni O,Cury PM,Toporcov TN,Paschoal AR,Durham AM

    更新日期:2015-06-24 00:00:00

  • Fraternal twins with Phelan-McDermid syndrome not involving the SHANK3 gene: case report and literature review.

    abstract:BACKGROUND:Phelan-McDermid syndrome (PMS, OMIM#606232), or 22q13 deletion syndrome, is a rare genetic disorder caused by deletion of the distal long arm of chromosome 22 with a variety of clinical features that display considerably heterogeneous degrees of severity. The SHANK3 gene is understood to be the critical gene...

    journal_title:BMC medical genomics

    pub_type: 杂志文章

    doi:10.1186/s12920-020-00802-0

    authors: Li S,Xi KW,Liu T,Zhang Y,Zhang M,Zeng LD,Li J

    更新日期:2020-10-06 00:00:00

  • A systems biology approach to construct the gene regulatory network of systemic inflammation via microarray and databases mining.

    abstract:BACKGROUND:Inflammation is a hallmark of many human diseases. Elucidating the mechanisms underlying systemic inflammation has long been an important topic in basic and clinical research. When primary pathogenetic events remains unclear due to its immense complexity, construction and analysis of the gene regulatory netw...

    journal_title:BMC medical genomics

    pub_type: 杂志文章

    doi:10.1186/1755-8794-1-46

    authors: Chen BS,Yang SK,Lan CY,Chuang YJ

    更新日期:2008-09-30 00:00:00

  • wtest: an integrated R package for genetic epistasis testing.

    abstract:BACKGROUND:With the increasing amount of high-throughput genomic sequencing data, there is a growing demand for a robust and flexible tool to perform interaction analysis. The identification of SNP-SNP, SNP-CpG, and higher order interactions helps explain the genetic etiology of human diseases, yet genome-wide analysis...

    journal_title:BMC medical genomics

    pub_type: 杂志文章

    doi:10.1186/s12920-019-0638-9

    authors: Sun R,Xia X,Chong KC,Zee BC,Wu WKK,Wang MH

    更新日期:2019-12-24 00:00:00

  • A systems biology approach to understand the pathophysiological mechanisms of cardiac pathological hypertrophy associated with rosiglitazone.

    abstract:BACKGROUND:Cardiac pathological hypertrophy is associated with a significantly increased risk of coronary heart disease and has been observed in diabetic patients treated with rosiglitazone whereas most published studies do not suggest a similar increase in risk of cardiovascular events in pioglitazone-treated diabetic...

    journal_title:BMC medical genomics

    pub_type: 杂志文章

    doi:10.1186/1755-8794-7-35

    authors: Verschuren L,Wielinga PY,Kelder T,Radonjic M,Salic K,Kleemann R,van Ommen B,Kooistra T

    更新日期:2014-06-17 00:00:00

  • CNAReporter: a GenePattern pipeline for the generation of clinical reports of genomic alterations.

    abstract:BACKGROUND:Genomic copy number alterations are widely associated with a broad range of human tumors and offer the potential to be used as a diagnostic tool. Especially in the emerging era of personalized medicine medical informatics tools that allow the fast visualization and analysis of genomic alterations of a patien...

    journal_title:BMC medical genomics

    pub_type: 杂志文章

    doi:10.1186/1755-8794-3-11

    authors: Kotliarov Y,Bozdag S,Cheng H,Wuchty S,Zenklusen JC,Fine HA

    更新日期:2010-04-09 00:00:00

  • Controlling the signal: Practical privacy protection of genomic data sharing through Beacon services.

    abstract:BACKGROUND:Genomic data is increasingly collected by a wide array of organizations. As such, there is a growing demand to make summary information about such collections available more widely. However, over the past decade, a series of investigations have shown that attacks, rooted in statistical inference methods, can...

    journal_title:BMC medical genomics

    pub_type: 杂志文章

    doi:10.1186/s12920-017-0282-1

    authors: Wan Z,Vorobeychik Y,Kantarcioglu M,Malin B

    更新日期:2017-07-26 00:00:00

  • Within-pair differences of DNA methylation levels between monozygotic twins are different between male and female pairs.

    abstract:BACKGROUND:DNA methylation levels will be important for detection of epigenetic effects. However, there are few reports showing sex-related differences in the sensitivity to DNA methylation. To evaluate their sex-related individual differences in the sensitivity to methylation rigorously, we performed a systematic anal...

    journal_title:BMC medical genomics

    pub_type: 杂志文章

    doi:10.1186/s12920-016-0217-2

    authors: Watanabe M,Honda C,Osaka Twin Research Group.,Iwatani Y,Yorifuji S,Iso H,Kamide K,Hatazawa J,Kihara S,Sakai N,Watanabe H,Makimoto K,Watanabe M,Honda C,Iwatani Y

    更新日期:2016-08-26 00:00:00

  • Characterization of global transcription profile of normal and HPV-immortalized keratinocytes and their response to TNF treatment.

    abstract:BACKGROUND:Persistent infection by high risk HPV types (e.g. HPV-16, -18, -31, and -45) is the main risk factor for development of cervical intraepithelial neoplasia and cervical cancer. Tumor necrosis factor (TNF) is a key mediator of epithelial cell inflammatory response and exerts a potent cytostatic effect on norma...

    journal_title:BMC medical genomics

    pub_type: 杂志文章

    doi:10.1186/1755-8794-1-29

    authors: Termini L,Boccardo E,Esteves GH,Hirata R Jr,Martins WK,Colo AE,Neves EJ,Villa LL,Reis LF

    更新日期:2008-06-27 00:00:00

  • Tiling resolution array CGH and high density expression profiling of urothelial carcinomas delineate genomic amplicons and candidate target genes specific for advanced tumors.

    abstract:BACKGROUND:Urothelial carcinoma (UC) is characterized by nonrandom chromosomal aberrations, varying from one or a few changes in early-stage and low-grade tumors, to highly rearranged karyotypes in muscle-invasive lesions. Recent array-CGH analyses have shed further light on the genomic changes underlying the neoplasti...

    journal_title:BMC medical genomics

    pub_type: 杂志文章

    doi:10.1186/1755-8794-1-3

    authors: Heidenblad M,Lindgren D,Jonson T,Liedberg F,Veerla S,Chebil G,Gudjonsson S,Borg A,Månsson W,Höglund M

    更新日期:2008-01-31 00:00:00

  • DNA methylation differences in monozygotic twin pairs discordant for schizophrenia identifies psychosis related genes and networks.

    abstract:BACKGROUND:Despite their singular origin, monozygotic twin pairs often display discordance for complex disorders including schizophrenia. It is a common (1%) and often familial disease with a discordance rate of ~50% in monozygotic twins. This high discordance is often explained by the role of yet unknown environmental...

    journal_title:BMC medical genomics

    pub_type: 杂志文章

    doi:10.1186/s12920-015-0093-1

    authors: Castellani CA,Laufer BI,Melka MG,Diehl EJ,O'Reilly RL,Singh SM

    更新日期:2015-05-06 00:00:00

  • Segmental neurofibromatosis type 2: discriminating two hit from four hit in a patient presenting multiple schwannomas confined to one limb.

    abstract:BACKGROUND:A clinical overlap exists between mosaic Neurofibromatosis Type 2 and sporadic Schwannomatosis conditions. In these cases a molecular analysis of tumors is recommended for a proper genetic diagnostics. This analysis is challenged by the fact that schwannomas in both conditions bear a somatic double inactivat...

    journal_title:BMC medical genomics

    pub_type: 杂志文章

    doi:10.1186/s12920-015-0076-2

    authors: Castellanos E,Bielsa I,Carrato C,Rosas I,Solanes A,Hostalot C,Amilibia E,Prades J,Roca-Ribas F,Lázaro C,Blanco I,Serra E,NF2 Multidisciplinary Clinics HUGTiP-ICO-IMPPC.

    更新日期:2015-01-24 00:00:00

  • Testicular sex cord-stromal tumor in a boy with 2q37 deletion syndrome.

    abstract:BACKGROUND:2q37 deletion syndrome is a rare congenital disorder that is characterized by facial dysmorphism, obesity, vascular and skeletal malformations, and a variable degree of intellectual disability. To date, common but variable phenotypes, such as skeletal or digit malformations and obesity, have been associated ...

    journal_title:BMC medical genomics

    pub_type: 杂志文章

    doi:10.1186/1755-8794-7-19

    authors: Sakai Y,Souzaki R,Yamamoto H,Matsushita Y,Nagata H,Ishizaki Y,Torisu H,Oda Y,Taguchi T,Shaw CA,Hara T

    更新日期:2014-04-22 00:00:00

  • A genome-wide association study of serum uric acid in African Americans.

    abstract:BACKGROUND:Uric acid is the primary byproduct of purine metabolism. Hyperuricemia is associated with body mass index (BMI), sex, and multiple complex diseases including gout, hypertension (HTN), renal disease, and type 2 diabetes (T2D). Multiple genome-wide association studies (GWAS) in individuals of European ancestry...

    journal_title:BMC medical genomics

    pub_type: 杂志文章

    doi:10.1186/1755-8794-4-17

    authors: Charles BA,Shriner D,Doumatey A,Chen G,Zhou J,Huang H,Herbert A,Gerry NP,Christman MF,Adeyemo A,Rotimi CN

    更新日期:2011-02-04 00:00:00

  • Host sequence motifs shared by HIV predict response to antiretroviral therapy.

    abstract:BACKGROUND:The HIV viral genome mutates at a high rate and poses a significant long term health risk even in the presence of combination antiretroviral therapy. Current methods for predicting a patient's response to therapy rely on site-directed mutagenesis experiments and in vitro resistance assays. In this bioinforma...

    journal_title:BMC medical genomics

    pub_type: 杂志文章

    doi:10.1186/1755-8794-2-47

    authors: Dampier W,Evans P,Ungar L,Tozeren A

    更新日期:2009-07-23 00:00:00

  • Development of somatic mutation signatures for risk stratification and prognosis in lung and colorectal adenocarcinomas.

    abstract:BACKGROUND:Prognostic signatures are vital to precision medicine. However, development of somatic mutation prognostic signatures for cancers remains a challenge. In this study we developed a novel method for discovering somatic mutation based prognostic signatures. RESULTS:Somatic mutation and clinical data for lung a...

    journal_title:BMC medical genomics

    pub_type: 杂志文章

    doi:10.1186/s12920-018-0454-7

    authors: Menor M,Zhu Y,Wang Y,Zhang J,Jiang B,Deng Y

    更新日期:2019-01-31 00:00:00

  • The Cancer Omics Atlas: an integrative resource for cancer omics annotations.

    abstract:BACKGROUND:The Cancer Genome Atlas (TCGA) is an important data resource for cancer biologists and oncologists. However, a lack of bioinformatics expertise often hinders experimental cancer biologists and oncologists from exploring the TCGA resource. Although a number of tools have been developed for facilitating cancer...

    journal_title:BMC medical genomics

    pub_type: 杂志文章

    doi:10.1186/s12920-018-0381-7

    authors: Sun Q,Li M,Wang X

    更新日期:2018-08-08 00:00:00

  • Identification of Chiari Type I Malformation subtypes using whole genome expression profiles and cranial base morphometrics.

    abstract:BACKGROUND:Chiari Type I Malformation (CMI) is characterized by herniation of the cerebellar tonsils through the foramen magnum at the base of the skull, resulting in significant neurologic morbidity. As CMI patients display a high degree of clinical variability and multiple mechanisms have been proposed for tonsillar ...

    journal_title:BMC medical genomics

    pub_type: 杂志文章

    doi:10.1186/1755-8794-7-39

    authors: Markunas CA,Lock E,Soldano K,Cope H,Ding CK,Enterline DS,Grant G,Fuchs H,Ashley-Koch AE,Gregory SG

    更新日期:2014-06-25 00:00:00

  • Validation of PhenX measures in the personalized medicine research project for use in gene/environment studies.

    abstract:BACKGROUND:The purpose of this paper is to describe the data collection efforts and validation of PhenX measures in the Personalized Medicine Research Project (PMRP) cohort. METHODS:Thirty-six measures were chosen from the PhenX Toolkit within the following domains: demographics; anthropometrics; alcohol, tobacco and ...

    journal_title:BMC medical genomics

    pub_type: 杂志文章

    doi:10.1186/1755-8794-7-3

    authors: McCarty CA,Berg R,Rottscheit CM,Waudby CJ,Kitchner T,Brilliant M,Ritchie MD

    更新日期:2014-01-14 00:00:00

  • Identification of lung cancer gene markers through kernel maximum mean discrepancy and information entropy.

    abstract:BACKGROUND:The early diagnosis of lung cancer has been a critical problem in clinical practice for a long time and identifying differentially expressed gene as disease marker is a promising solution. However, the most existing gene differential expression analysis (DEA) methods have two main drawbacks: First, these met...

    journal_title:BMC medical genomics

    pub_type: 杂志文章

    doi:10.1186/s12920-019-0630-4

    authors: Zhao Z,Peng H,Zhang X,Zheng Y,Chen F,Fang L,Li J

    更新日期:2019-12-20 00:00:00

  • What is the right sequencing approach? Solo VS extended family analysis in consanguineous populations.

    abstract:BACKGROUND:Testing strategies is crucial for genetics clinics and testing laboratories. In this study, we tried to compare the hit rate between solo and trio and trio plus testing and between trio and sibship testing. Finally, we studied the impact of extended family analysis, mainly in complex and unsolved cases. MET...

    journal_title:BMC medical genomics

    pub_type: 杂志文章

    doi:10.1186/s12920-020-00743-8

    authors: Alfares A,Alsubaie L,Aloraini T,Alaskar A,Althagafi A,Alahmad A,Rashid M,Alswaid A,Alothaim A,Eyaid W,Ababneh F,Albalwi M,Alotaibi R,Almutairi M,Altharawi N,Alsamer A,Abdelhakim M,Kafkas S,Mineta K,Cheung N,Abdall

    更新日期:2020-07-17 00:00:00

  • Pan-cancer analysis of differential DNA methylation patterns.

    abstract:BACKGROUND:DNA methylation is a key epigenetic regulator contributing to cancer development. To understand the role of DNA methylation in tumorigenesis, it is important to investigate and compare differential methylation (DM) patterns between normal and case samples across different cancer types. However, current pan-c...

    journal_title:BMC medical genomics

    pub_type: 杂志文章

    doi:10.1186/s12920-020-00780-3

    authors: Shi M,Tsui SK,Wu H,Wei Y

    更新日期:2020-10-22 00:00:00

  • Integrative analysis reveals disease-associated genes and biomarkers for prostate cancer progression.

    abstract:BACKGROUND:Prostate cancer is one of the most common complex diseases with high leading cause of death in men. Identifications of prostate cancer associated genes and biomarkers are thus essential as they can gain insights into the mechanisms underlying disease progression and advancing for early diagnosis and developi...

    journal_title:BMC medical genomics

    pub_type: 杂志文章

    doi:10.1186/1755-8794-7-S1-S3

    authors: Li Y,Vongsangnak W,Chen L,Shen B

    更新日期:2014-01-01 00:00:00

  • A computational procedure for functional characterization of potential marker genes from molecular data: Alzheimer's as a case study.

    abstract:BACKGROUND:A molecular characterization of Alzheimer's Disease (AD) is the key to the identification of altered gene sets that lead to AD progression. We rely on the assumption that candidate marker genes for a given disease belong to specific pathogenic pathways, and we aim at unveiling those pathways stable across ti...

    journal_title:BMC medical genomics

    pub_type: 杂志文章

    doi:10.1186/1755-8794-4-55

    authors: Squillario M,Barla A

    更新日期:2011-07-05 00:00:00

  • Modified entropy-based procedure detects gene-gene-interactions in unconventional genetic models.

    abstract:BACKGROUND:Since it is assumed that genetic interactions play an important role in understanding the mechanisms of complex diseases, different statistical approaches have been suggested in recent years for this task. One interesting approach is the entropy-based IGENT method by Kwon et al. that promises an efficient de...

    journal_title:BMC medical genomics

    pub_type: 杂志文章

    doi:10.1186/s12920-020-0703-4

    authors: Malten J,König IR

    更新日期:2020-04-23 00:00:00

  • Role of caveolin 1, E-cadherin, Enolase 2 and PKCalpha on resistance to methotrexate in human HT29 colon cancer cells.

    abstract:BACKGROUND:Methotrexate is one of the earliest cytotoxic drugs used in cancer therapy, and despite the isolation of multiple other folate antagonists, methotrexate maintains its significant role as a treatment for different types of cancer and other disorders. The usefulness of treatment with methotrexate is limited by...

    journal_title:BMC medical genomics

    pub_type: 杂志文章

    doi:10.1186/1755-8794-1-35

    authors: Selga E,Morales C,Noé V,Peinado MA,Ciudad CJ

    更新日期:2008-08-11 00:00:00

  • ProGeo-neo: a customized proteogenomic workflow for neoantigen prediction and selection.

    abstract:BACKGROUND:Neoantigens can be differentially recognized by T cell receptor (TCR) as these sequences are derived from mutant proteins and are unique to the tumor. The discovery of neoantigens is the first key step for tumor-specific antigen (TSA) based immunotherapy. Based on high-throughput tumor genomic analysis, each...

    journal_title:BMC medical genomics

    pub_type: 杂志文章

    doi:10.1186/s12920-020-0683-4

    authors: Li Y,Wang G,Tan X,Ouyang J,Zhang M,Song X,Liu Q,Leng Q,Chen L,Xie L

    更新日期:2020-04-03 00:00:00

  • HIP2: an online database of human plasma proteins from healthy individuals.

    abstract:BACKGROUND:With the introduction of increasingly powerful mass spectrometry (MS) techniques for clinical research, several recent large-scale MS proteomics studies have sought to characterize the entire human plasma proteome with a general objective for identifying thousands of proteins leaked from tissues in the circu...

    journal_title:BMC medical genomics

    pub_type: 杂志文章

    doi:10.1186/1755-8794-1-12

    authors: Saha S,Harrison SH,Shen C,Tang H,Radivojac P,Arnold RJ,Zhang X,Chen JY

    更新日期:2008-04-25 00:00:00