scholarly journals Identification and Mapping of a 2,009-bp DNA Deletion inSERPING1of a Hereditary Angioedema Patient

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Wai-Yu Wong ◽  
Helen Wong ◽  
Elaine Au ◽  
Eric Chan
Keyword(s):  
Hereditary Angioedema ◽  
Genomic Dna ◽  
Epigastric Pain ◽  
Molecular Techniques ◽  
Type I ◽  
Base Pairs ◽  
Dna Deletion ◽  
Dna Deletions ◽  
Left And Right ◽  
Dependent Probe

We report a heterozygous, 2,009 base pairs (bps) genomic DNA deletion within theSERPING1gene that has not previously been reported in a case of type I hereditary angioedema (HAE). The patient is a 28-year-old Han Chinese female living in Hong Kong who has suffered from recurrent angioedema since adolescence, with increasing attack frequency as she entered adulthood; in the past, episodes occurred annually, but now occur every two to three months. The affected areas are not itchy and include common sites such as the left and right forearms, but without throat involvement. The patient also experiences epigastric pain. The patient’s mother suffers from similar symptoms. A mutation in the serine protease inhibitor, clade G, member 1 (SERPING1) gene is associated with HAE. Patients with HAE type I commonly carry either a small deletion withinSERPING1or a truncated transcript. We performed a multiplex ligation-dependent probe amplification (MLPA) assay on our indexed patient. Our result suggests a 2,009 bps deletion spanning across exons 5 and 6 withinSERPING1. Although earlier literature has described other large DNA deletions encasing exons 5 and 6 inSERPING1, these DNA rearrangements were larger in size between 4 and 6 kbps, and the breakpoint locations were generally not determined due to technical constraints (Pappalardo et al., 2000; Duponchel et al., 2001; Roche et al., 2005; Loules et al., 2018; and Göβwein et al., 2008). Our report describes mapping of this 2,009 bps inSERPING1. Using a combination of molecular techniques, we were able to confirm and locate this large heterozygous genomic DNA deletion that includes both exons 5 and 6 ofSERPING1.

scholarly journals Genetic Diversity of Salvia Species Assessed by ISSR and RAPD Markers

2016 ◽  
Vol 44 (2) ◽  
pp. 431-436 ◽  
Author(s):  
Masoumeh YOUSEFIAZARKHANIAN ◽  
Ali ASGHARI ◽  
Jafar AHMADI ◽  
Behvar ASGHARI ◽  
Ali Ashraf JAFARI
Keyword(s):  
Genetic Diversity ◽  
Genetic Polymorphisms ◽  
Genomic Dna ◽  
Rapd Markers ◽  
Genetic Relationships ◽  
Genetic Variations ◽  
Molecular Techniques ◽  
Wild Populations ◽  
Similarity Coefficients ◽  
The World

The genus Salvia includes an enormous assemblage of nearly 1,000 species dispersed around the world. Due to possible threats to this genus, there is an immediate requirement to evaluate the diversity of its wild populations. ISSR and RAPD molecular techniques were used to evaluate the genetic relationships among twenty-one ecotypes of eight Salvia species. Amplification of genomic DNA using 23 primers (15 RAPD and eight ISSR) produced 280 bands, of which 91% were polymorphic. The results of marker parameters showed no clear difference between two marker systems. It was generally observed that both ISSR and RAPD markers had similar efficiency in detecting genetic polymorphisms with remarkable ability to differentiate the closely related ecotypes of Salvia. Nei’s similarity coefficients for these techniques ranged from 0.48 to 0.98. Based on the results of clustering, PCoA and AMOVA, the genetic diversity between and within species was confirmed. So, conservation and domestication of the genus Salvia must be due to levels of genetic variations.

scholarly journals An evidence-based review of the potential role of icatibant in the treatment of acute attacks in hereditary angioedema type I and II

Core Evidence ◽  
2012 ◽  
pp. 105 ◽  
Author(s):  
Bernard Floccard ◽  
Hautin ◽  
Laurence Bouillet ◽  
Coppere ◽  
Allaouchiche
Keyword(s):  
Hereditary Angioedema ◽  
Potential Role ◽  
Evidence Based ◽  
Type I ◽  
Acute Attacks

scholarly journals Outcomes of long term treatments of type I hereditary angioedema in a Turkish family

2017 ◽  
Vol 92 (5) ◽  
pp. 655-660 ◽  
Author(s):  
Gulsen Akoglu ◽  
Belgin Kesim ◽  
Gokhan Yildiz ◽  
Ahmet Metin
Keyword(s):  
Hereditary Angioedema ◽  
Type I ◽  
Turkish Family

scholarly journals Diabetic polyneuropathy: features of the clinical picture and electroneuromyographic parameters in the presence of comorbidity

2020 ◽  
pp. 39-49
Author(s):  
V. M. Dubynetska
Keyword(s):  
Clinical Picture ◽  
Type I Diabetes ◽  
Diabetic Polyneuropathy ◽  
Neurological Status ◽  
Control Group ◽  
Type I ◽  
Abductor Hallucis ◽  
Fiber Damage ◽  
Left And Right ◽  
Group B

Knowledges of certain key moments in the clinical course of diabetic polyneuropathy (DP) combined with varied comorbidity will allow the disease to be identified more effectively and treated comprehensively at different stages of onset. The aim of the research: was to investigate and summarize the features of the clinical picture, electroneuromyographic parameters in patients with DP in the presence of comorbidity. Materials and methods. 111 patients aged 19 to 69 years with DP were examined. The patients were divided into two groups: DP due to type I diabetes mellitus (DM) (group A; n = 61) and type II (group B; n = 50). According to the detected comorbidity, the following subgroups were identified: persons with DP as the result of type I, II DM with only one pathology (subgroup 1; n = 53) and the presence of multimorbidity (two or more pathologies) (subgroup 2; n = 21). The control group – 30 healthy persons representative by age and gender, 37 patients with DP without comorbidity. The patients were examined for neurological status, laboratory tests, instrumental examination methods. Results and discussion. In general, among the studied groups, the lowest nerve conduction velocity in the motor fibers was in abductor hallucis, tibialis on the left, extensor digitorum brevis, peroneus on the left and right, in sensory fibers – peroneus superficialis on the left and right, n. suralis on the left and right. Such changes primarily reflect the lesion of the distal extremities, which clinically looks like a distal symmetrical DP. Was dominated axonal and demyelinating type of nerve fiber damage. Conclusions. Comorbidity contributes to the progression of DP and deterioration of its clinical picture, electroneuromyographic rates, even in the presence of a single pathology, low duration of DM and HbA1c level.

scholarly journals CryoEM structures of MDA5-dsRNA filaments at different stages of ATP hydrolysis

2018 ◽  
Author(s):  
Qin Yu ◽  
Kun Qu ◽  
Yorgo Modis
Keyword(s):  
Rna Binding ◽  
Atp Hydrolysis ◽  
Type I ◽  
List Type ◽  
Base Pairs ◽  
Nucleotide Analogs ◽  
Double Stranded Rna ◽  
Transition State Analogs ◽  
Helical Twist ◽  
Dsrna Binding

SummaryDouble-stranded RNA (dsRNA) is a potent proinflammatory signature of viral infection. Long cytosolic dsRNA is recognized by MDA5. The cooperative assembly of MDA5 into helical filaments on dsRNA nucleates the assembly of a multiprotein type-I-interferon signaling platform. Here, we determined cryoEM structures of MDA5-dsRNA filaments with different helical twists and bound nucleotide analogs, at resolutions sufficient to build and refine atomic models. The structures identify the filament forming interfaces, which encode the dsRNA binding cooperativity and length specificity of MDA5. The predominantly hydrophobic interface contacts confer flexibility, reflected in the variable helical twist within filaments. Mutation of filament-forming residues can result in loss or gain of signaling activity. Each MDA5 molecule spans 14 or 15 RNA base pairs, depending on the twist. Variations in twist also correlate with variations in the occupancy and type of nucleotide in the active site, providing insights on how ATP hydrolysis contributes to MDA5-dsRNA recognition.eTOCStructures of MDA5 bound to double-stranded RNA reveal a flexible, predominantly hydrophobic filament forming interface. The filaments have variable helical twist. Structures determined with ATP and transition state analogs show how the ATPase cycle is coupled to changes in helical twist, the mode of RNA binding and the length of the RNA footprint of MDA5.HighlightsCryoEM structures of MDA5-dsRNA filaments determined for three catalytic statesFilament forming interfaces are flexible and predominantly hydrophobicMutation of filament-forming residues can cause loss or gain of IFN-β signalingATPase cycle is coupled to changes in filament twist and size of the RNA footprint

Hereditary angioedema: Pathophysiology (HAE type I, HAE type II, and HAE nC1-INH)

2020 ◽  
Vol 41 (6) ◽  
pp. S14-S17 ◽  
Author(s):  
H. James Wedner
Keyword(s):  
Serine Protease ◽  
Hereditary Angioedema ◽  
Normal Activity ◽  
Genetic Alterations ◽  
Type I ◽  
Factor Xii ◽  
Kinin System ◽  
Major Pathway ◽  
Major Mechanism ◽  
Kallikrein Kinin System

The pathophysiology of hereditary angioedema (HAE) in virtually all cases is the result of the uncontrolled production of the vasoactive peptide bradykinin. C1 inhibitor (C1-INH) is a serine protease inhibitor, which, under normal circumstances, is the regulator of critical enzymes that are active in the cascades that result in bradykinin generation. In the classic forms of HAE, C1-INH is not produced in sufficient quantities (<40% of normal) or the function is <40% of normal activity. The major pathway for the production of bradykinin is the “contact system,” also known as the kallikrein-kinin system. This system begins with the activation of factor XII (FXII) to FXIIa, by a variety of physiologic and pathologic stimuli. FXIIa is a serine protease that binds to surfaces and cleaves prekallikrein to the active serine protease kallikrein. Kallikrein then cleaves high-molecular-weight kininogen to release the nonapeptide bradykinin. Bradykinin binds to the bradykinin β2 receptor, which increases vascular permeability and allows the flow of fluids into the extracellular space and results in angioedema. The two major enzymes generated in this cascade FXIIa and kallikrein are inhibited by C1-INH, which is the major regulator of this cascade. Failure to adequately control the production of bradykinin is thus the major mechanism for HAE. Several other types of HAE in which C1-INH is not decreased (HAE nlC1-INH) have been described. The alterations in FXII and plasminogen (also a serine protease inhibited by C1-INH) like with classic HAE are the result of dysregulation of bradykinin generation. Only genetic alterations in angiopoietin-1 may not be related to bradykinin generation, rather related to the control of the effect of bradykinin on the vascular endothelium.

scholarly journals Identification of molecular defects in a subject with type I CD36 deficiency

Blood ◽  
1994 ◽  
Vol 83 (12) ◽  
pp. 3545-3552 ◽  
Author(s):  
H Kashiwagi ◽  
Y Tomiyama ◽  
S Kosugi ◽  
M Shiraga ◽  
RH Lipsky ◽  
...  
Keyword(s):  
Genomic Dna ◽  
Stop Codon ◽  
Type I ◽  
Molecular Defects ◽  
Cdna Sequences ◽  
Cd36 Deficiency ◽  
Translation Stop Codon ◽  
Polymerase Chain ◽  
Exon 4 ◽  
Splice Junctions

Abstract We performed a molecular analysis of a subject whose platelets and monocytes did not express any cell surface CD36 (designated as a type I CD36 deficiency). Amplification of the 5′ half of platelet and monocyte CD36cDNA (corresponding to nucleotide [nt] 191–1009 of the published CD36 cDNA sequence [Oquendo et al, Cell, 58:95, 1989]) showed that two different-sized CD36 cDNAs existed. One cDNA was of predicted normal size, whereas the other was about 150 bp smaller than that predicted for normal CD36 cDNA. Amplification of the 3′ region of CD36 cDNA (nt 962–1714) in this subject showed only normal-sized CD36 cDNA. Cloning and nt sequence analysis of the cDNAs showed that the smaller sized CD36 cDNA had 161-bp deletion (from nt 331 to 491), and a dinucleotide deletion starting at nt position 539. The same dinucleotide deletion was also detected in the normal sized CD36 cDNA. Both deletions caused a frameshift leading to the appearance of a translation stop codon. RNA blot analysis and quantitative assay using the reverse transcription- polymerase chain reaction (RT-PCR) showed that the CD36 transcripts in both platelets and monocytes were greatly reduced. Comparison of the determined cDNA sequences with the genomic DNA sequence for the human CD36 gene showed that the dinucleotide deletion was located in exon 5, and that the 161-bp deletion corresponded to a loss of exon 4. PCR- based analysis using genomic DNA showed that this subject was homozygous for the dinucleotide deletion in exon 5. Except for the dinucleotide deletion, we could not find any abnormalities around exon 3, 4, and 5 including the splice junctions. These results suggested that the deletions in CD36 mRNA were likely to be responsible for instability of the transcripts, and the dinucleotide deletion in exon 5 might affect the splicing of exon 4.

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