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1.
G3 (Bethesda) ; 11(8)2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-34849816

RESUMO

Resistance breeding is an effective approach against wheat stem rust caused by Puccinia graminis f. sp. tritici (Pgt). The synthetic hexaploid wheat line Largo (pedigree: durum wheat "Langdon" × Aegilops tauschii PI 268210) was found to have resistance to a broad spectrum of Pgt races including the Ug99 race group. To identify the stem rust resistance (Sr) genes, we genotyped a population of 188 recombinant inbred lines developed from a cross between the susceptible wheat line ND495 and Largo using the wheat Infinium 90 K SNP iSelect array and evaluated the population for seedling resistance to the Pgt races TTKSK, TRTTF, and TTTTF in the greenhouse conditions. Based on genetic linkage analysis using the marker and rust data, we identified six quantitative trait loci (QTL) with effectiveness against different races. Three QTL on chromosome arms 6AL, 2BL, and 2BS corresponded to Sr genes Sr13c, Sr9e, and a likely new gene from Langdon, respectively. Two other QTL from PI 268210 on 2DS and 1DS were associated with a potentially new allele of Sr46 and a likely new Sr gene, respectively. In addition, Sr7a was identified as the underlying gene for the 4AL QTL from ND495. Knowledge of the Sr genes in Largo will help to design breeding experiments aimed to develop new stem rust-resistant wheat varieties. Largo and its derived lines are particularly useful for introducing two Ug99-effective genes Sr13c and Sr46 into modern bread wheat varieties. The 90 K SNP-based high-density map will be useful for identifying the other important genes in Largo.

2.
Cancers (Basel) ; 13(23)2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34885041

RESUMO

Gastric cancer is a leading cause of death from cancer globally. Gastric cancer is classified into intestinal, diffuse and indeterminate subtypes based on histology according to the Laurén classification. The intestinal and diffuse subtypes, although different in histology, demographics and outcomes, are still treated in the same fashion. This study was designed to discover proteomic signatures of diffuse and intestinal subtypes. Mass spectrometry-based proteomics using tandem mass tags (TMT)-based multiplexed analysis was used to identify proteins in tumor tissues from patients with diffuse or intestinal gastric cancer with adjacent normal tissue control. A total of 7448 or 4846 proteins were identified from intestinal or diffuse subtype, respectively. This quantitative mass spectrometric analysis defined a proteomic signature of differential expression across the two subtypes, which included gremlin1 (GREM1), bcl-2-associated athanogene 2 (BAG2), olfactomedin 4 (OLFM4), thyroid hormone receptor interacting protein 6 (TRIP6) and melanoma-associated antigen 9 (MAGE-A9) proteins. Although GREM1, BAG2, OLFM4, TRIP6 and MAGE-A9 have all been previously implicated in tumor progression and metastasis, they have not been linked to intestinal or diffuse subtypes of gastric cancer. Using immunohistochemical labelling of a tissue microarray comprising of 124 cases of gastric cancer, we validated the proteomic signature obtained by mass spectrometry in the discovery cohort. Our findings should help investigate the pathogenesis of these gastric cancer subtypes and potentially lead to strategies for early diagnosis and treatment.

3.
Molecules ; 26(23)2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34885888

RESUMO

Although numerous studies have demonstrated the biological and multifaceted nature of dimethyl sulfoxide (DMSO) across different in vitro models, the direct effect of "non-toxic" low DMSO doses on cardiac and cancer cells has not been clearly explored. In the present study, H9c2 cardiomyoblasts and MCF-7 breast cancer cells were treated with varying concentrations of DMSO (0.001-3.7%) for 6 days. Here, DMSO doses < 0.5% enhanced the cardiomyoblasts respiratory control ratio and cellular viability relative to the control cells. However, 3.7% DMSO exposure enhanced the rate of apoptosis, which was driven by mitochondrial dysfunction and oxidative stress in the cardiomyoblasts. Additionally, in the cancer cells, DMSO (≥0.009) led to a reduction in the cell's maximal respiratory capacity and ATP-linked respiration and turnover. As a result, the reduced bioenergetics accelerated ROS production whilst increasing early and late apoptosis in these cells. Surprisingly, 0.001% DMSO exposure led to a significant increase in the cancer cells proliferative activity. The latter, therefore, suggests that the use of DMSO, as a solvent or therapeutic compound, should be applied with caution in the cancer cells. Paradoxically, in the cardiomyoblasts, the application of DMSO (≤0.5%) demonstrated no cytotoxic or overt therapeutic benefits.

4.
Indian J Surg Oncol ; : 1-7, 2021 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-34924731

RESUMO

COVID pandemic has impacted cancer care delivery and cancer surgical services globally. There is an urgent need to study the extent of the impact of COVID on cancer surgery and individual institutional response and strategies adopted to counter the adverse impact. A review of administrative and clinical policy changes adopted at the tertiary cancer center to combat COVID pandemic and resume cancer surgical services were performed. A retrospective comparative analysis of cancer out-patient census during COVID pandemic affected year and the preceding normal year along with cancer surgery data audit for the same periods was performed to assess the impact of the pandemic on cancer surgery. In addition, COVID infection rates among cancer surgery patients and healthcare workers were evaluated. There was approximately a 50% reduction in cancer outpatient registrations during COVID pandemic affected year. A trend of increasing footfalls was noted with decreasing COVID intensity and opening of lockdowns. There was a 33% reduction in major elective surgery and a 41% reduction in emergency surgery performed during the COVID period. As far as cancer surgeries are concerned, there was a 12-50% reduction in volumes involving different subsites. Overall COVID positivity rates among cancer surgery patients was low (8.17%), and approximately 30% of healthcare workers involved in cancer surgery were tested positive for COVID during the study period. Results of the current study indicate a significant impact of COVID pandemic on cancer surgical services. There was a significant impact on outpatient visits and cancer surgery volumes. However, a multidisciplinary-coordinated team approach, effective administrative and policy implementation, adoption of revised surgical safety and anesthesia protocols, COVID screening, and testing protocols facilitated resumption of cancer surgical services without adverse impact on surgical outcomes.

5.
J Parkinsons Dis ; 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34897099

RESUMO

BACKGROUND: Glucocerebrosidase gene (GBA) mutations influence risk and prognosis of Parkinson's disease (PD), possibly through accumulation of glycosphingolipids, including glucosylceramide (GL-1). Venglustat is a novel, brain penetrant glucosylceramide synthase inhibitor. OBJECTIVE: Evaluate venglustat pharmacology, safety, and tolerability in patients with PD and GBA mutations (GBA-PD). METHODS: Part 1 of the phase 2 MOVES-PD trial (NCT02906020) was a randomized, double-blinded, placebo-controlled, dose-escalation study performed in six countries. Eligible participants included Japanese and non-Japanese patients aged 18-80 years with PD diagnosis and heterozygous GBA mutation. Participants were randomized to three doses of once-daily oral venglustat or placebo and were followed up to 36 weeks (Japanese participants: 52 weeks). Primary endpoint was venglustat safety and tolerability versus placebo. Secondary and exploratory endpoints included venglustat pharmacokinetics and pharmacodynamics. RESULTS: Participants (N = 29) received venglustat (Japanese, n = 9; non-Japanese, n = 13) or placebo (n = 3; n = 4). Eight (89%) Japanese and 12 (92%) non-Japanese venglustat-treated participants experienced at least one adverse event (AE) versus two (67%) and four (100%) participants from the respective placebo groups. Most AEs were mild or moderate; no serious AEs or deaths occurred. Two venglustat-treated non-Japanese participants discontinued due to AEs (confusional state and panic attack). Over 4 weeks, venglustat exposure in plasma and cerebrospinal fluid (CSF) increased, and GL-1 levels in plasma and CSF decreased, both in a dose-dependent manner. At the highest dose, CSF GL-1 decreased by 72.0% in Japanese and 74.3% in non-Japanese participants. CONCLUSION: Venglustat showed favorable safety and tolerability in MOVES-PD Part 1 and target engagement was achieved in CSF.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34831841

RESUMO

Recent scientific trends have revealed that the collection and analysis of data on the occurrence and fate of SARS-CoV-2 in wastewater may serve as an early warning system for COVID-19. In South Africa, the first COVID-19 epicenter emerged in the Western Cape Province. The City of Cape Town, located in the Western Cape Province, has approximately 4 million inhabitants. This study reports on the monitoring of SARS-CoV-2 RNA in the wastewater of the City of Cape Town's wastewater treatment plants (WWTPs) during the peak of the epidemic. During this period, the highest overall median viral RNA signal was observed in week 1 (9200 RNA copies/mL) and declined to 127 copies/mL in week 6. The overall decrease in the amount of detected viral SARS-CoV-2 RNA over the 6-week study period was associated with a declining number of newly identified COVID-19 cases in the city. The SARS-CoV-2 early warning system has now been established to detect future waves of COVID-19.

7.
Ann Indian Acad Neurol ; 24(4): 580-585, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34728954

RESUMO

Introduction: Stroke is the most common cause of epilepsy in the adult population. Post-stroke seizures (PSSs) are classified into early-onset seizures (ES) and late-onset (LS). ES can significantly affect the clinical outcome and occurrence of LS. Methods: We analyzed data from a prospective cohort of acute ischemic stroke patients between June 2018 and May 2020 in a neurology unit at a tertiary hospital. We screened all acute stroke patients and included consecutive patients older than 18 years of age, presenting with acute, first-ever neuroimaging-confirmed ischemic stroke. We excluded patients with a previous stroke, transient ischemic attacks, hemorrhagic stroke, cerebral venous thrombosis, prior history of seizures, or any other epileptogenic comorbidity. ES were classified as spontaneous seizures occurring within 1 week of the stroke. The main outcome assessed was the occurrence of ES. The secondary outcome was to determine predictors of ES and create an ES prediction score. Results: We screened 432 patients; of them, 291 were enrolled. ES occurred in 37 patients (12.7%). Cortical location (OR: 4.2), large artery disease subtype (OR: 2.9), mRS at presentation (OR: 1.4), use of anticoagulants (OR: 2.6), and hypertension (OR: 0.3) were significantly associated with the occurrence of ES. Patients with ES had a statistically significant worse clinical outcome at 3 months follow-up (P = 0.0072). Conclusion: We could formulate an ES prediction tool using the following components: (a) cortical location, (b) large vessel stroke, (c) mRS at admission, (d) anticoagulant use, and (e) presence of hypertension. This tool might help in treating patients at high risk for ES with prophylactic ASD, thereby preventing seizures and their complications.

8.
J Am Coll Cardiol ; 78(19): 1919-1929, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34736568

RESUMO

Socioeconomic disparities in cardiovascular risk factors and outcomes exist among women, particularly those of minority racial or ethnic backgrounds. Barriers to optimal cardiovascular health begin early in life-with inadequate access to effective contraception, postpartum follow-up, and maternity leave-and result in excess rates of myocardial infarction, stroke, and cardiovascular death in at-risk populations. Contributing factors include reduced access to care, low levels of income and social support, and lack of diversity among cardiology clinicians and within clinical trials. These barriers can be mitigated by optimizing care access via policy change and improving physical access to care in women with geographic or transportation limitations. Addressing structural racism through policy change and bolstering structured community support systems will be key to reducing adverse cardiovascular outcomes among women of racial and ethnic minorities. Diversification of the cardiology workforce to more closely represent the patients we serve will be beneficial to all women.

9.
Front Mol Biosci ; 8: 727070, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34708073

RESUMO

Biosurfactants are surface-active molecules produced by microorganisms, either on the cell surface or secreted extracellularly. They form a thin film on the surface of microorganisms and help in their detachment or attachment to other cell surfaces. They are involved in regulating the motility of bacteria and quorum sensing. Here, we describe the various types of biosurfactants produced by microorganisms and their role in controlling motility, antagonism, virulence, and cellular communication.

10.
Cureus ; 13(8): e16929, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34513500

RESUMO

Lipomas are benign lesions of adipose tissue, which commonly affect the soft tissues but are rarely found in the musculoskeletal system. Intraosseous lipomas are rare benign tumors and even rarer in calcaneum, only to be found incidentally in the majority of cases. We report a case of a 45-year-old male patient who presented to the outpatient department with complaints of bilateral heel pain, which was initially treated conservatively as the presentation was similar to plantar fasciitis. On further follow-up, a plain radiograph of the ankles was taken, which showed a lytic lesion of the calcaneum with mild sclerotic margins on the right side with normal left foot radiographs. On magnetic resonance imaging, the lytic lesion demonstrated hyperintense signals on T1-weighted sagittal images, characteristic of fatty tissue, which helped us in arriving at the diagnosis of an intraosseous lipoma. The patient was treated by conservative means with physiotherapy, which relieved the pain, and on serial follow-ups, the lesion was found non-progressive on successive radiological evaluation. The differential diagnosis of such an entity includes plantar fasciitis, tumors such as an aneurysmal bone cyst, bone infarct, etc. With the increasing use of magnetic resonance imaging and computed tomography scans, physicians should be aware of the possibility of an intraosseous lipoma of the calcaneum, which should be ruled out during evaluation. Although possible, malignant pathology or aggressive transformation of such lesions is very rare; however, the lesion should be evaluated adequately and managed by surgical means in cases non-responsive to various conservative modalities.

11.
Cureus ; 13(8): e17570, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34513529

RESUMO

Tuberculous pachymeningitis is a rare disease that should be suspected in patients with chronic headaches, focal neurological signs, and magnetic resonance imaging (MRI) findings of dural thickening. We report the case of a 62-year-old male who presented with chronic headaches for over a year, progressive right-sided vision and hearing loss for six months, and progressive dysphagia for a month. On investigation, MRI showed dural thickening, cerebrospinal fluid showed lymphocytic pleocytosis with high protein and normal glucose levels, and biopsy of the dural matter showed necrotizing granulomas with Langhans giant cells. The patient responded well to antitubercular treatment and steroids. Follow-up MRI 24 months later showed almost complete resolution of meningeal enhancement. Though tuberculosis is an uncommon cause of pachymeningitis, it should be considered, as it responds well to treatment.

12.
Sex Transm Dis ; 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34561371

RESUMO

ABSTRACT: We adapted a simple hydroxylamine-based indole assay to detect indole from stored vaginal swab specimens from women with and without bacterial vaginosis (BV). Women with BV had significantly higher vaginal indole levels compared to women without BV (6451.5 µM vs. 5632.4 µM; P = 0.01), suggesting that indole-producing bacteria are a component of BV.

13.
J Hum Hypertens ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34526646

RESUMO

This cross-sectional study examined the prevalence, stages, subtypes of hypertension, and the associated risk factors in adolescent school children in Western India. We screened 2,644 adolescents, from 10 different private and government schools in urban and rural areas for hypertension, as defined by the 2017 Clinical Practice Guidelines. The association of stages and subtypes with age, gender, body mass index, type of school, and place of residence was analysed. 197 children (7.5%) had hypertension; 170 (6.4%) had stage I, 27 (1%) had stage II and 76 (2.9%) had elevated blood pressure (EBP). The risk of EBP was higher in children > 15 years of age (p = 0.006). Compared with normal-weight children, obese, and overweight children had a higher risk of hypertension [odds ratio (OR) 9 (5.84, 13.88) and 3.77 (2.59, 5.48) respectively], whereas underweight children had a lower risk [OR 0.39 (0.16, 0.98)]. Normal-weight hypertension was seen in 5.2% and was higher in children from government schools (9.4%). Systolic-diastolic hypertension (SDH) was the most common subtype, seen in 136 (5.1%). SDH was more common in girls, in rural children, and in those with stage II hypertension. Isolated diastolic hypertension, seen in 51 (1.9%), was more common in boys, in urban children, and in those with EBP.

14.
J Cell Commun Signal ; 15(4): 595-600, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34487344

RESUMO

Severe acute respiratory syndrome coronaviruses (SARS-CoVs) caused worldwide epidemics over the past few decades. Extensive studies on various strains of coronaviruses provided a basic understanding of the pathogenesis of the disease. Presently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is leading a global pandemic with unprecedented challenges. This is the third coronavirus outbreak of this century. A signaling pathway map of signaling events induced by SARS-CoV infection is not yet available. In this study, we present a literature-annotated signaling pathway map of reactions induced by SARS-CoV infected cells. Multiple signaling modules were found to be orchestrated including PI3K-AKT, Ras-MAPK, JAK-STAT, Type 1 IFN and NFκB. The signaling pathway map of SARS-CoV consists of 110 molecules and 101 reactions mediated by SARS-CoV proteins. The pathway reaction data are available in various community standard data exchange formats including Systems Biology Graphical Notation (SBGN). The pathway map is publicly available through the GitHub repository and data in various formats can be freely downloadable.

15.
Asian J Transfus Sci ; 15(1): 30-36, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34349454

RESUMO

BACKGROUND: As a part of continuous quality initiatives, while moving from triple bags to quadruple bags, we undertook a study to compare platelet-rich plasma (PRP) and buffy-coat (BC) methods with respect to all blood components (red blood cells [RBCs], random donor platelet concentrate [RDPC], and fresh frozen plasma [FFP]) prepared by PRP and BC methods. MATERIALS AND METHODS: It was a prospective analysis of different physical and quality parameters of RDPC, RBC, and FFP prepared out of 100 whole blood (WB) donations. Of these, 50 WB units were processed by PRP method using Triple bags and 50 WB units by BC method, using quadruple (top and bottom) bags, with an attached integral filter. RESULTS: RBC prepared by BC method had higher hematocrit (61.3 ± 1.91% vs. 56.03 ± 3.37%; P < 0.05) and lower white blood cell (WBC) contamination (6.3 × 104 ± 6.1 vs. 5.41 × 105 ± 2.5; P < 0.05) in comparison to prepared by PRP method. Higher PLT yield (7.67 × 1010 ± 1.8 vs. 6.47 × 1010 ± 1.5; P < 0.05) and lower WBC count (8.24 × 103 ± 1.1 vs. 1.5 × 104 ± 2.1; P < 0.05) was observed in RDPC prepared by BC method than PRP derived. CD62P expression was lower in RDPC prepared by BC method (31.46 ± 9.7%; P < 0.05) as compared to PRP method (43.35 ± 12.5%; P < 0.05). The BC method also resulted in increased plasma yield (210.56 ± 18.54 ml vs. 187.92 ± 12.93 ml; P < 0.05) in FFP in comparison to PRP method. CONCLUSION: The blood components produced from WB by the BC method have laboratory variables suggestive of superior quality than those produced by the PRP method.

16.
East Mediterr Health J ; 27(7): 728-737, 2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34369588

RESUMO

Background: Afghanistan is grappling with high burden of malnutrition in women and children and a rising burden of noncommunicable diseases. Aims: A narrative review was conducted with the aim of mapping current nutrition policies and capacity development initiatives to assess policy and the institutional environment and identify gaps and opportunities. Methods: A comprehensive, broad based search was conducted, including databases and websites and policy and programme documents. Results: The policy focuses on multisectoral efforts to address nutrition challenges; however; implementation of nutrition-specific and nutrition-sensitive interventions is not delivered uniformly at the community level due to continued conflic situations and geographic inaccessibility, lack of availability of trained human resources and weak institutions. There is limited evidence on the effectiveness of nutrition programmes in Afghanistan. Limited policy provisions are available to address nutrition issues due to the rising burden of noncommunicable diseases, urbanization and changing dietary patterns. The shortage of skilled nutritional professionals is a critical issue. Lack of institutional capacity, educational standards and accreditation mechanism poses major challenges. Ongoing training programmes are fragmented and fail to meet the requirements of a professional nutrition workforce. Conclusion: The findings highlight that well-structured policies and strategies focusing on maternal and child nutrition provide an enabling policy environment to scale up nutrition interventions. Evidence on the implementation of programmes is needed to aid policy recommendations. The lack of an institutional mechanism for professional nutrition education highlights the great need for action in Afghanistan for public health nutrition and education.


Assuntos
Estado Nutricional , Saúde Pública , Afeganistão , Fortalecimento Institucional , Criança , Feminino , Humanos , Política Nutricional
18.
Br J Clin Pharmacol ; 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34449087

RESUMO

AIMS: The prevalence of vitamin D deficiency is high in children with chronic kidney disease (CKD). However, current dosing recommendations are based on limited pharmacokinetic (PK) data. This study aimed to develop a population PK model of colecalciferol that can be used to optimise colecalciferol dosing in this population. METHODS: Data from 83 children with CKD were used to develop a population PK model using a nonlinear mixed effects modelling approach. Serum creatinine and type of kidney disease (glomerular vs. nonglomerular disease) were investigated as covariates, and optimal dosing was determined based on achieving and maintaining 25-hydroxyvitamin D (25(OH)D) concentration of 30-48 ng/mL. RESULTS: The time course of 25(OH)D concentrations was best described by a 1-compartment model with the addition of a basal concentration parameter to reflect endogenous 25(OH)D production from diet and sun exposure. Colecalciferol showed wide between-subject variability in its PK, with total body weight scaled allometrically the only covariate included in the model. Model-based simulations showed that current dosing recommendations for colecalciferol can be optimised using a weight-based dosing strategy. CONCLUSION: This is the first study to describe the population PK of colecalciferol in children with CKD. PK model informed dosing is expected to improve the attainment of target 25(OH)D concentrations, while minimising the risk of overdosing.

19.
Nat Commun ; 12(1): 4358, 2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34272367

RESUMO

Premature termination codons (PTCs) prevent translation of a full-length protein and trigger nonsense-mediated mRNA decay (NMD). Nonsense suppression (also termed readthrough) therapy restores protein function by selectively suppressing translation termination at PTCs. Poor efficacy of current readthrough agents prompted us to search for better compounds. An NMD-sensitive NanoLuc readthrough reporter was used to screen 771,345 compounds. Among the 180 compounds identified with readthrough activity, SRI-37240 and its more potent derivative SRI-41315, induce a prolonged pause at stop codons and suppress PTCs associated with cystic fibrosis in immortalized and primary human bronchial epithelial cells, restoring CFTR expression and function. SRI-41315 suppresses PTCs by reducing the abundance of the termination factor eRF1. SRI-41315 also potentiates aminoglycoside-mediated readthrough, leading to synergistic increases in CFTR activity. Combining readthrough agents that target distinct components of the translation machinery is a promising treatment strategy for diseases caused by PTCs.


Assuntos
Códon sem Sentido/antagonistas & inibidores , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Células Epiteliais/efeitos dos fármacos , Degradação do RNAm Mediada por Códon sem Sentido , Terminação Traducional da Cadeia Peptídica/efeitos dos fármacos , Fatores de Terminação de Peptídeos/metabolismo , Aminoglicosídeos/metabolismo , Códon sem Sentido/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Células Epiteliais/metabolismo , Genes Reporter , Gentamicinas/farmacologia , Células HEK293 , Humanos , Microssomos Hepáticos/efeitos dos fármacos , Fatores de Terminação de Peptídeos/genética , Complexo de Endopeptidases do Proteassoma/efeitos dos fármacos , Complexo de Endopeptidases do Proteassoma/metabolismo , Interferência de RNA , Ribossomos/metabolismo , Relação Estrutura-Atividade
20.
Indian J Nephrol ; 31(2): 182-186, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34267444

RESUMO

Atypical haemolytic uremic syndrome (aHUS) is a clinically and genetically heterogeneous condition caused by a complex interplay between genomic susceptibility factors and environmental influences. Pathogenic variants in the DGKE gene are recently identified in cases with infantile-onset autosomal recessive aHUS. The presence of low serum C3 levels, however, has rarely been described in cases of DGKE-associated aHUS. Molecular genetic testing was performed by a commercial next-generation sequencing (NGS) panel as well and by an in-house developed targeted NGS for DGKE gene. Copy number variations (CNVs) were computed from NGS data by calculating a normalised copy number ratio of aligned number of reads at targeted genomic regions against multiple reference regions of the same sample and multiple controls. We report here two such novel clinically relevant variants (c.727_730delTTGT and c.251_259delGCGCCTTC) in the DGKE gene, in two families of infantile aHUS with low serum C3 levels.

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