scholarly journals A Rare Mutation in The APOB Gene Associated with Neurological Manifestations in Familial Hypobetalipoproteinemia

2020 ◽  
Vol 21 (4) ◽  
pp. 1439
Author(s):  
Joanna Musialik ◽  
Anna Boguszewska-Chachulska ◽  
Dorota Pojda-Wilczek ◽  
Agnieszka Gorzkowska ◽  
Robert Szymańczak ◽  
...  
Keyword(s):  
Clinical Signs ◽  
Neurological Symptoms ◽  
Sequencing Analysis ◽  
Coding Region ◽  
Apob Gene ◽  
Missense Variants ◽  
Splicing Variant ◽  
Electrophysiological Tests ◽  
Familial Hypobetalipoproteinemia ◽  
Next Generation Sequencing Ngs

Clinical phenotypes of familial hypobetalipoproteinemia (FHBL) are related to a number of defective apolipoprotein B (APOB) alleles. Fatty liver disease is a typical manifestation, but serious neurological symptoms can appear. In this study, genetic analysis of the APOB gene and ophthalmological diagnostics were performed for family members with FHBL. Five relatives with FHBL, including a proband who developed neurological disorders, were examined. A sequencing analysis of the whole coding region of the APOB gene, including flanking intronic regions, was performed using the next-generation sequencing (NGS) method. Electrophysiological ophthalmological examinations were also done. In the proband and his affected relatives, NGS identified the presence of the pathogenic, rare heterozygous splicing variant c.3696+1G>T. Two known heterozygous missense variants—c.2188G>A, p.(Val730Ile) and c.8353A>C, p.(Asn2785His)—in the APOB gene were also detected. In all patients, many ophthalmologic abnormalities in electrophysiological tests were also found. The identified splicing variant c.3696+1G>T can be associated with observed autosomal, dominant FHBL with coexisting neurological symptoms, and both identified missense variants could be excluded as the main cause of observed clinical signs, according to mutation databases and the literature. Electroretinography examination is a sensitive method for the detection of early neuropathy and should therefore be recommended for the care of patients with FHBL.

scholarly journals Otitis and meningoencephalitis associated with infectious coryza (Avibacterium paragallinarum) in commercial broiler chickens

2018 ◽  
Vol 30 (5) ◽  
pp. 784-788 ◽  
Author(s):  
Manuela Crispo ◽  
C. Gabriel Sentíes-Cué ◽  
George L. Cooper ◽  
Grace Mountainspring ◽  
Charles Corsiglia ◽  
...  
Keyword(s):  
Broiler Chickens ◽  
Animal Health ◽  
Clinical Signs ◽  
Economic Losses ◽  
Laboratory System ◽  
Sequencing Analysis ◽  
Contributing Factors ◽  
Infectious Coryza ◽  
Avibacterium Paragallinarum ◽  
Commercial Broiler

Infectious coryza, caused by Avibacterium paragallinarum, is an acute respiratory disease of poultry that can result in substantial morbidity, mortality, and economic losses. In March 2017, the Turlock branch of the California Animal Health and Food Safety laboratory system encountered an unusual clinical and pathologic presentation of infectious coryza in 6 live, 29-d-old, commercial broiler chickens that were submitted for diagnostic investigation. Antemortem evaluation revealed severe neurologic signs, including disorientation, torticollis, and opisthotonos. Swollen head–like syndrome and sinusitis were also present. Histologically, severe sinusitis, cranial osteomyelitis, otitis media and interna, and meningoencephalitis were noted, explaining the clinical signs described. A. paragallinarum was readily isolated from the upper and lower respiratory tract, brain, and cranial bones. Infectious bronchitis virus (IBV) was also detected by PCR, and IBV was isolated in embryonated chicken eggs. Based on sequencing analysis, the IBV appeared 99% homologous to strain CA1737. A synergistic effect between A. paragallinarum and IBV, resulting in exacerbation of clinical signs and increased mortality, may have occurred in this case. A. paragallinarum should be considered among the possible causes of neurologic signs in chickens. Appropriate media should be used for bacterial isolation, and the role of additional contributing factors and/or complicating agents should be investigated in cases of infectious coryza.

scholarly journals Rare Presentation of Toxoplasma Pneumonitis in the Absence of Neurological Symptoms in an AIDS Patient and Use of Next-Generation Sequencing for Diagnosis

2020 ◽  
Author(s):  
Moni Roy ◽  
Nikhut Siddique ◽  
Bindu Bathina ◽  
Sharjeel Ahmad
Keyword(s):  
Next Generation Sequencing ◽  
Opportunistic Infections ◽  
Miliary Tuberculosis ◽  
Neurological Symptoms ◽  
Pneumocystis Jirovecii Pneumonia ◽  
Next Generation ◽  
Rare Presentation ◽  
Immunodeficiency Syndrome ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Toxoplasma gondii is a known cause of encephalitis in human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients. Toxoplasma pneumonitis is a manifestation of extracerebral toxoplasmosis and can be clinically indistinguishable from other opportunistic infections including Pneumocystis jirovecii pneumonia (PJP) and miliary tuberculosis. In this case report, Toxoplasma pneumonitis and disseminated toxoplasmosis was diagnosed using next-generation sequencing (NGS) and polymerase chain reaction (PCR) assessment. NGS can detect microbial cell-free DNA (cfDNA) circulating in the plasma of over 1,000 pathogens. This case is a rare presentation of Toxoplasma pneumonitis in the absence of neurological symptoms and we discuss the use of NGS of microbial cfDNA and PCR tests that may be utilized for the timely diagnosis of such challenging cases.

scholarly journals Diagnosis of Severe Tetanus Assisted by Next-Generation Sequencing Analysis of Etiology: A Case Report

2020 ◽  
Author(s):  
Yuling An ◽  
Mingming Fan ◽  
Ziyu Li ◽  
You Peng ◽  
Xiaomeng Yi ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Comprehensive Treatment ◽  
Sequencing Analysis ◽  
Next Generation ◽  
Next Generation Sequencing Analysis ◽  
Autonomic Instability ◽  
The Right ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing ◽  
Severe Tetanus

Abstract We shared our successful treatment experience of a severe tetanus patient in China. A 50 year old male patient was admitted to our hospital 10 days after the right arm injury due to pain and masticatory weakness. The pathogen of wound secretion was confirmed to be clostridium tetanus by next-generation sequencing (NGS).The patient's condition rapidly progressed to a severe state with autonomic instability. After debridement and comprehensive treatment in ICU, including deep analgesia and sedation with dexmedetomidine, ventilator support and anti-infection treatment, the patient finally recovered and discharged. This case suggested that early diagnosis and reasonable intervention of severe tetanus could reduce mortality.

scholarly journals ViennaNGS: A toolbox for building efficient next- generation sequencing analysis pipelines

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 50 ◽  
Author(s):  
Michael T. Wolfinger ◽  
Jörg Fallmann ◽  
Florian Eggenhofer ◽  
Fabian Amman
Keyword(s):  
Next Generation Sequencing ◽  
Sequence Motif ◽  
Software Components ◽  
Sequencing Analysis ◽  
Next Generation ◽  
File Formats ◽  
Next Generation Sequencing Analysis ◽  
Next Generation Sequencing Ngs ◽  
Ngs Data ◽  
Generation Sequencing

Recent achievements in next-generation sequencing (NGS) technologies lead to a high demand for reuseable software components to easily compile customized analysis workflows for big genomics data. We present ViennaNGS, an integrated collection of Perl modules focused on building efficient pipelines for NGS data processing. It comes with functionality for extracting and converting features from common NGS file formats, computation and evaluation of read mapping statistics, as well as normalization of RNA abundance. Moreover, ViennaNGS provides software components for identification and characterization of splice junctions from RNA-seq data, parsing and condensing sequence motif data, automated construction of Assembly and Track Hubs for the UCSC genome browser, as well as wrapper routines for a set of commonly used NGS command line tools.

scholarly journals Incidental Finding of a Homozygous p.M348K Asymptomatic Italian Patient Confirms the Many Faces of Cystic Fibrosis

2015 ◽  
Vol 2015 ◽  
pp. 1-4
Author(s):  
Rossana Molinario ◽  
Sara Palumbo ◽  
Paola Concolino ◽  
Sandro Rocchetti ◽  
Roberta Rizza ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Incidental Finding ◽  
Pancreatic Insufficiency ◽  
Normal Male ◽  
Transmembrane Conductance Regulator ◽  
Coding Region ◽  
Multiple Organs ◽  
Rare Polymorphism ◽  
The Many ◽  
Next Generation Sequencing Ngs

Cystic fibrosis (CF; OMIM number 219700) is an autosomal recessive disease caused by mutations in theCFTR(cystic fibrosis transmembrane conductance regulator) gene, which results in abnormal viscous mucoid secretions in multiple organs and whose main clinical features are pancreatic insufficiency, chronic endobronchial infection, and male infertility. We report the case of a 47-year-old apparently normal male resulting in homozygosity for the mutation p.M348K from nonconsanguineous parents. The proband was screened using a standard panel of 70 different tested on NanoChip 400 platform. The massive parallel pyrosequencing on 454 JS machine allowed the second level analysis. The patient was firstly screened with two different platforms available in our laboratory, obtaining an ambiguous signal for the p.R347P mutation. For this reason we decided to clarify the discordant result ofCFTRstatus by Next Generation Sequencing (NGS) using 454 Junior instrument. The patient is resulted no carrier of the p.R347P mutation, but NGS highlighted a homozygous substitution from T>A at position 1043 in the coding region, causing an amino acid substitution from methionine to lysine (p.M348K). Casual finding of p.M348K homozygote mutation in an individual, without any feature of classical or nonclassical CF form, allowed us to confirm that p.M348K is a benign rare polymorphism.

scholarly journals Relevance of Titin Missense and Non-Frameshifting Insertions/Deletions Variants in Dilated Cardiomyopathy

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Oyediran Akinrinade ◽  
Tiina Heliö ◽  
Ronald H. Lekanne Deprez ◽  
Jan D. H. Jongbloed ◽  
Ludolf G. Boven ◽  
...  
Keyword(s):  
Dilated Cardiomyopathy ◽  
Human Disease ◽  
Disease Gene ◽  
Reference Population ◽  
Population Database ◽  
Missense Variants ◽  
Clinical Diagnostic ◽  
Significant Enrichment ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Abstract Recent advancements in next generation sequencing (NGS) technology have led to the identification of the giant sarcomere gene, titin (TTN), as a major human disease gene. Truncating variants of TTN (TTNtv) especially in the A-band region account for 20% of dilated cardiomyopathy (DCM) cases. Much attention has been focused on assessment and interpretation of TTNtv in human disease; however, missense and non-frameshifting insertions/deletions (NFS-INDELs) are difficult to assess and interpret in clinical diagnostic workflow. Targeted sequencing covering all exons of TTN was performed on a cohort of 530 primary DCM patients from three cardiogenetic centres across Europe. Using stringent bioinformatic filtering, twenty-nine and two rare TTN missense and NFS-INDELs variants predicted deleterious were identified in 6.98% and 0.38% of DCM patients, respectively. However, when compared with those identified in the largest available reference population database, no significant enrichment of such variants was identified in DCM patients. Moreover, DCM patients and reference individuals had comparable frequencies of splice-region missense variants with predicted splicing alteration. DCM patients and reference populations had comparable frequencies of rare predicted deleterious TTN missense variants including splice-region missense variants suggesting that these variants are not independently causative for DCM. Hence, these variants should be classified as likely benign in the clinical diagnostic workflow, although a modifier effect cannot be excluded at this stage.

scholarly journals Novel PITX2 Mutations including a Mutation Causing an Unusual Ophthalmic Phenotype of Axenfeld-Rieger Syndrome

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Liqin Huang ◽  
Yong Meng ◽  
Xiangming Guo
Keyword(s):  
Genomic Dna ◽  
Anterior Segment ◽  
Dominant Negative ◽  
Chinese Patients ◽  
Dominant Negative Effect ◽  
Sequencing Analysis ◽  
Coding Region ◽  
Direct Dna Sequencing ◽  
Rieger Syndrome ◽  
Pitx2 Gene

Purpose. The aims of this study were to examine novel mutations in PITX2 and FOXC1 in Chinese patients with anterior segment dysgenesis (ASD) and to compare the clinical presentations of these mutations with previously reported associated phenotypes. Methods. Twenty-six unrelated patients with different forms of ASD were enrolled from our paediatric and genetic eye clinic. The ocular manifestations of both eyes of each patient were recorded. Genomic DNA was prepared from venous leukocytes. All coding exons of PITX2 and FOXC1 were amplified by polymerase chain reaction (PCR) from genomic DNA and subjected to direct DNA sequencing. Analysis of mutations in control subjects was performed by heteroduplex single-strand conformation polymorphism (SSCP) analysis. Results. Sequence analysis of the PITX2 gene revealed four mutations, including c.475_476delCT (P.L159VfsX39), c.64C > T (P.Q22X), c.296delG (P.R99PfsX56), and c.206G > A (P.R69H). The first three mutations were found to be novel. The c.475_476delCT (P.L159VfsX39) mutation, located at the 3′ end of the PITX2-coding region, was identified in a Chinese Axenfeld-Rieger syndrome (ARS) patient who presented with an unusual severe phenotype of bilateral aniridia. The clinical characteristics, including the severity and manifestations of the patient’s phenotype, were compared with reported PITX2-associated aniridia phenotypes of ARS in the literature. Conclusions. These results expand the mutation spectrum of the PITX2 gene in patients with ARS. The PITX2 gene may be responsible for a significant portion of ARS with additional systemic defects in the Chinese population. This is the first reported case of a mutation at the 3′ end of the PITX2-coding region extending the phenotypic consequences to bilateral aniridia. The traits of ARS could display tremendous variability in severity and manifestations due to the dominant-negative effect of PITX2. Our results further emphasize the importance of careful clinical and genetic analysis in determining mutation-disease associations and may lead to a better understanding of the role of PITX2 in ocular development.

Familial hypobetalipoproteinemia: Analysis of three Spanish cases with two new mutations in the APOB gene

Gene ◽  
2013 ◽  
Vol 531 (1) ◽  
pp. 92-96 ◽  
Author(s):  
R. Martín-Morales ◽  
J.D. García-Díaz ◽  
P. Tarugi ◽  
P. González-Santos ◽  
P. Saavedra-Vallejo ◽  
...  
Keyword(s):  
Apob Gene ◽  
Familial Hypobetalipoproteinemia ◽  
New Mutations
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