3,543 results match your criteria milder phenotypes

Asymptomatic COVID-19: disease tolerance with efficient anti-viral immunity against SARS-CoV-2.

EMBO Mol Med 2021 May 7:e14045. Epub 2021 May 7.

A*STAR Infectious Disease Labs (A*STAR ID Labs), Agency for Science, Technology and Research, 8A Biomedical Grove, Immunos, Singapore, 138648.

The immune responses and mechanisms limiting symptom progression in asymptomatic cases of SARS-CoV-2 infection remain unclear. We comprehensively characterized transcriptomic profiles, cytokine responses, neutralization capacity of antibodies and cellular immune phenotypes of asymptomatic patients with acute SARS-CoV-2 infection to identify potential protective mechanisms. Compared to symptomatic patients, asymptomatic patients had higher counts of mature neutrophils and lower proportion of CD169+ expressing monocytes in the peripheral blood. Read More

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Lrp5 mutant and crispant zebrafish faithfully model human osteoporosis, establishing the zebrafish as a platform for CRISPR-based functional screening of osteoporosis candidate genes.

J Bone Miner Res 2021 May 6. Epub 2021 May 6.

Center for Medical Genetics Ghent, Department of Biomolecular Medicine, Ghent University, Ghent, Belgium.

Genome-wide association studies (GWAS) have improved our understanding of the genetic architecture of common, complex diseases such as osteoporosis. Nevertheless, to attribute functional skeletal contributions of candidate genes to osteoporosis-related traits there is a need for efficient and cost-effective in vivo functional testing. This can be achieved through CRISPR-based reverse genetic screens, where phenotyping is traditionally performed in stable germline KO mutants. Read More

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Evidence of under-reporting of early-onset preeclampsia using register data.

Paediatr Perinat Epidemiol 2021 May 6. Epub 2021 May 6.

Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.

Background: Early-onset preeclampsia, traditionally defined as presenting before 34 gestational weeks, is associated with even higher risks of perinatal death, placental abruption, and stroke, than late-onset preeclampsia.

Objective: We estimated the degree of misclassification in a high-risk population of lupus pregnancies and a general population comparator when gestational age at delivery defined preeclampsia phenotype compared to first preeclampsia diagnosis.

Methods: Patients with lupus and general population comparators from Sweden with ≥1 singleton pregnancy in the Medical Birth Register with a documented ICD code for preeclampsia were included (2002-2016). Read More

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Compound heterozygous p. Arg949Trp and p. Gly970Ala mutations deteriorated the function of PEX1p: A study on PEX1 in a patient with Zellweger syndrome.

J Cell Biochem 2021 May 6. Epub 2021 May 6.

Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Postal Code 81746-73441, Iran.

The peroxisome is responsible for a variety of vital pathways in primary metabolism, including the very long-chain fatty-acid oxidation and plasmalogen lipid biosynthesis. Autosomal recessive disorder of the Zellweger spectrum (ZSD) is a major subset of peroxisome biogenesis disorders (PBDs) that can be caused by mutations in any of the 14 PEX genes. Zellweger syndrome (ZS) is the foremost common and severe phenotype within the heterogeneous ZSD. Read More

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Pulmonary Hypertension: The Hidden Danger for Newborns.

Steven H Abman

Neonatology 2021 May 5:1-7. Epub 2021 May 5.

Pediatric Pulmonary Medicine, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, Colorado, USA.

Despite growing awareness of the clinical importance of pulmonary hypertension (PH) in preterm infants, uncertainty persists regarding the different clinical settings in which abnormalities of pulmonary vascular growth, function, and structure contribute to high morbidity and mortality, and potential interventions to improve outcomes are uncertain. A major gap for improving outcomes of preterm infants with PH has been the limited characterization of the distinct settings of PH and related disease-specific mechanisms in preterm infants that represent diverse pulmonary vascular phenotypes of prematurity. In comparison with term newborns, preterm infants have a higher risk for developing hypoxemia due to suprasystemic levels of PH in preterm infants shortly after birth or persistent pulmonary hypertension of the newborn (PPHN). Read More

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The molecular and phenotypic spectrum of CLCN4-related epilepsy.

Epilepsia 2021 May 5. Epub 2021 May 5.

Institute of Chemistry and Biochemistry, Berlin Free University, Berlin, Germany.

Objective: This study was undertaken to expand the phenotypic and genetic spectrum of CLCN4-related epilepsy and to investigate genotype-phenotype correlations.

Methods: We systematically reviewed the phenotypic and genetic spectrum of newly diagnosed and previously reported patients with CLCN4-related epilepsy. Three novel variants identified in four patients reported in this study were evaluated through in silico prediction and functional analysis by Western blot, immunofluorescence, and electrophysiological measurements. Read More

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Cyclic alternating pattern in obstructive sleep apnea: A preliminary study.

J Sleep Res 2021 May 3:e13350. Epub 2021 May 3.

Department of Neuroimaging, Sleep and Brain Plasticity Centre, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, UK.

Obstructive sleep apnea is linked to cardiovascular disease, metabolic disorders and dementia. The precise nature of the association between respiratory events in obstructive sleep apnea, cortical or subcortical arousals, and cognitive, autonomic and oxidative stress consequences remains incompletely elucidated. Previous studies have aimed to understand the relationship between obstructive sleep apnea and arousal patterns, as defined by the cyclic alternating pattern, but results have been inconsistent, in part likely due to the presence of associated comorbidities. Read More

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Coronavirus disease 2019 respiratory disease in children: clinical presentation and pathophysiology.

Curr Opin Pediatr 2021 06;33(3):302-310

Division of Pulmonary, Asthma and Sleep Medicine, Department of Pediatrics, Center for Excellence in Pulmonary Biology, Stanford University Medical School, Stanford, California, USA.

Purpose Of Review: Pediatric coronavirus disease 2019 (COVID-19) respiratory disease is a distinct entity from adult illness, most notable in its milder phenotype. This review summarizes the current knowledge of the clinical patterns, cellular pathophysiology, and epidemiology of COVID-19 respiratory disease in children with specific attention toward factors that account for the maturation-related differences in disease severity.

Recent Findings: Over the past 14 months, knowledge of the clinical presentation and pathophysiology of COVID-19 pneumonia has rapidly expanded. Read More

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Management of chronic pulmonary disease in the time of coronavirus disease 2019.

Curr Opin Pediatr 2021 06;33(3):294-301

Division of Pulmonary and Sleep Medicine, Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA.

Purpose Of Review: The purpose of this review is to discuss the most recent data describing the impact of coronavirus disease 2019 (COVID-19) on the pediatric population with chronic pulmonary disease. We specifically focus on children with asthma, cystic fibrosis (CF), and lung transplant recipients.

Recent Findings: Children with asthma, CF, and lung transplant recipients do not appear to have an increased risk of morbidity or mortality with COVID-19 infection compared to the general pediatric population. Read More

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Idiopathic Peripheral Retinal Telangiectasia in Adults: A Case Series and Literature Review.

Maciej Gawęcki

J Clin Med 2021 Apr 19;10(8). Epub 2021 Apr 19.

Dobry Wzrok Ophthalmological Clinic, 80-822 Gdansk, Poland.

Idiopathic peripheral retinal telangiectasia (IPT), often termed as Coats disease, can present in a milder form with the onset in adulthood. The goal of this case series study and literature review was to describe and classify different presenting forms and treatment of this entity and to review contemporary methods of its management. Six cases of adult onset IPT were described with the following phenotypes based on fundus ophthalmoscopy, fluorescein angiography, and optical coherence tomography findings: IPT without exudates or foveal involvement, IPT with peripheral exudates without foveal involvement, IPT with peripheral exudates and cystoid macular edema, and IPT with peripheral and macular hard exudates. Read More

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Peroxisomal Disorders and Their Mouse Models Point to Essential Roles of Peroxisomes for Retinal Integrity.

Int J Mol Sci 2021 Apr 15;22(8). Epub 2021 Apr 15.

Lab of Cell Metabolism, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, 3000 Leuven, Belgium.

Peroxisomes are multifunctional organelles, well known for their role in cellular lipid homeostasis. Their importance is highlighted by the life-threatening diseases caused by peroxisomal dysfunction. Importantly, most patients suffering from peroxisomal biogenesis disorders, even those with a milder disease course, present with a number of ocular symptoms, including retinopathy. Read More

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Risk phenotypes of diabetes and association with COVID-19 severity and death: a living systematic review and meta-analysis.

Diabetologia 2021 Apr 28. Epub 2021 Apr 28.

German Center for Diabetes Research (DZD), Partner Düsseldorf, Düsseldorf, Germany.

Aims/hypothesis: Diabetes has been identified as a risk factor for poor prognosis of coronavirus disease-2019 (COVID-19). The aim of this study is to identify high-risk phenotypes of diabetes associated with COVID-19 severity and death.

Methods: This is the first edition of a living systematic review and meta-analysis on observational studies investigating phenotypes in individuals with diabetes and COVID-19-related death and severity. Read More

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Prognosis of patients treated in a single neurosurgical reference centre for brain metastasis caused by dormant disseminated cells.

Oncol Lett 2021 Jun 8;21(6):454. Epub 2021 Apr 8.

Department of Neurosurgery, Erasmus Hospital, Free University of Bruxelles, B-1070 Brussels, Belgium.

Brain metastasis (BM) is a frequent complication of systemic cancer usually associated with poor prognosis. Survival depends on numerous factors, which complicates prognosis and treatment. It has been suggested that BM growing from previously dormant disseminated tumour cells (DTCs) may exhibit a milder phenotype than BM derived from continuously progressing metastatic cells; however, to the best of our knowledge, the prognosis of patients presenting with BM from dormant DTCs is unknown. Read More

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Clinical and inflammatory characteristics of patients with asthma in the Spanish MEGA project cohort.

Clin Transl Allergy 2021 Mar;11(1):e12001

Servicio de Alergología, Departamento de Inmunología, Instituto de Investigación Sanitaria (IIS) Fundación Jiménez Díaz, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain.

Introduction: The MEGA (MEchanism underlying the Genesis and evolution of Asthma) project is a multicenter cohort study carried out in eight Spanish hospitals, gathering clinical, physiological, and molecular data from patients with asthma and multimorbidities in order to gain insight into the different physiopathological mechanisms involved in this disorder.

Material And Methods: We report the baseline clinical and physiological characteristics and biomarker measures of adult participants in the project with the aim of better understanding the natural history and underlying mechanisms of asthma as well as the associated multimorbidities across different levels of severity. We carried out a detailed clinical examination, pulmonary function testing, measurement of fractional exhaled nitric oxide (FeNO), blood counts, induced sputum, skin prick tests, chest computed tomography scan, asthma questionnaires, and multimorbidity assessment in 512 asthmatic patients. Read More

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Pre-clinical dose-escalation studies establish a therapeutic range for U7snRNA-mediated exon 2 skipping.

Mol Ther Methods Clin Dev 2021 Jun 23;21:325-340. Epub 2021 Mar 23.

Center for Gene Therapy, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH 43205, USA.

Duchenne muscular dystrophy (DMD) is an X-linked progressive disease characterized by loss of dystrophin protein that typically results from truncating mutations in the DMD gene. Current exon-skipping therapies have sought to treat deletion mutations that abolish an open reading frame (ORF) by skipping an adjacent exon, in order to restore an ORF that allows translation of an internally deleted yet partially functional protein, as is seen with many patients with the milder Becker muscular dystrophy (BMD) phenotype. In contrast to that approach, skipping of one copy of a duplicated exon would be expected to result in a full-length transcript and production of a wild-type protein. Read More

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Selective Requirements for Vascular Endothelial Cells and Circulating Factors in the Regulation of Retinal Neurogenesis.

Front Cell Dev Biol 2021 8;9:628737. Epub 2021 Apr 8.

Department of Biological Sciences, University of Idaho, Moscow, ID, United States.

Development of the vertebrate eye requires signaling interactions between neural and non-neural tissues. Interactions between components of the vascular system and the developing neural retina have been difficult to decipher, however, due to the challenges of untangling these interactions from the roles of the vasculature in gas exchange. Here we use the embryonic zebrafish, which is not yet reliant upon hemoglobin-mediated oxygen transport, together with genetic strategies for (1) temporally-selective depletion of vascular endothelial cells, (2) elimination of blood flow through the circulation, and (3) elimination of cells of the erythroid lineage, including erythrocytes. Read More

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Health related quality of life and psychological parameters in different polycystic ovary syndrome phenotypes: a comparative cross-sectional study.

J Ovarian Res 2021 Apr 24;14(1):57. Epub 2021 Apr 24.

Department of Reproductive Health and Midwifery, Faculty of Medical Sciences, Tarbiat Modares University, Jalal Al-Ahmad Highway, Nasr Bridge, Tehran, Iran.

Background: Polycystic Ovary Syndrome (PCOS) is associated with high levels of phsychological implications and detriments to Quality of Life (QoL). The aim of this study was to assess Health- Related Quality of Life (HRQoL), depression, and anxiety in Iranian women with different PCOS phenotypes.

Methods: The present observational, cross-sectional study was carried out on 239 PCOS women who were classified on the basis of Rotterdam criteria into four categories: A (n = 77), B (n = 38), C (n = 68), and D (n = 56). Read More

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Phenotypes of SMA patients retaining SMN1 with intragenic mutation.

Brain Dev 2021 Apr 20. Epub 2021 Apr 20.

Department of Community Medicine and Social Healthcare Science, Kobe University Graduate School of Medicine, Kobe, Japan. Electronic address:

Background: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by homozygous deletion or intragenic mutation of the SMN1 gene. It is well-known that high copy number of its homologous gene, SMN2, modifies the phenotype of SMN1-deleted patients. However, in the patients with intragenic SMN1 mutation, the relationship between phenotype and SMN2 copy number remains unclear. Read More

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Recessive LOXHD1 variants cause a prelingual down-sloping hearing loss: genotype-phenotype correlation and three additional children with novel variants.

Int J Pediatr Otorhinolaryngol 2021 Apr 20;145:110715. Epub 2021 Apr 20.

Department of Otolaryngology-Head and Neck Surgery, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China. Electronic address:

Background: Biallelic mutations in LOXHD1 have been identified as the cause of DFNB77 (deafness, autosomal recessive 77). It is a new progressive, severe-to-profound, and late-onset nonsyndromic sensorineural hearing loss (NSHL), and is highly heterogeneous genetically and phenotypically. This study aimed to provide an additional three cases of DFNB77. Read More

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Associations Between Variant Repeat Interruptions and Clinical Outcomes in Myotonic Dystrophy Type 1.

Neurol Genet 2021 Apr 9;7(2):e572. Epub 2021 Mar 9.

Department of Neurology (S.W., K.G., B.S.), Friedrich-Baur-Institute, Ludwig-Maximilians-Universität München, Germany; Institute of Molecular, Cell and Systems Biology (S.A.C., D.G.M.), University of Glasgow, United Kingdom; Department of Neurology (K.O., B.G.M.v.E.), Radboud University, Nijmegen, The Netherlands; Institute of Genetic Medicine (A.C.J.-M.), Institute for Ageing and Health, Newcastle University, United Kingdom; Neuromuscular Reference Centre (F.D., G.B.), Assistance Publique-Hôpitaux de Paris, France; Department of Neuropediatrics and Muscle Disorders (H.L.), University of Freiburg, Breisgau, Germany; Center for Genomic Regulation (H.L.), Barcelona Institute of Science and Technology, Spain; Tayside Clinical Trials Unit (F.H.), The University of Dundee, United Kingdom; and Department of Medical Psychology (H.K.), Amsterdam University Medical Centers, University of Amsterdam, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands.

Objective: To assess the association between variant repeat (VR) interruptions in patients with myotonic dystrophy type 1 (DM1) and clinical symptoms and outcome measures after cognitive behavioral therapy (CBT) intervention.

Methods: Adult patients with DM1 were recruited within the OPTIMISTIC trial (NCT02118779). Disease-related history, current clinical symptoms and comorbidities, functional assessments, and disease- and health-related questionnaires were obtained at baseline and after 5 and 10 months. Read More

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Association of Dual LRRK2 G2019S and GBA Variations With Parkinson Disease Progression.

JAMA Netw Open 2021 Apr 1;4(4):e215845. Epub 2021 Apr 1.

Department of Neurology, Mount Sinai Beth Israel, and Icahn School of Medicine, Mount Sinai, New York, New York.

Importance: Despite a hypothesis that harboring a leucine-rich repeat kinase 2(LRRK2) G2019S variation and a glucocerebrosidase (GBA) variant would have a combined deleterious association with disease pathogenesis, milder clinical phenotypes have been reported in dual LRRK2 and GBA variations Parkinson disease (PD) than in GBA variation PD alone.

Objective: To evaluate the association of LRRK2 G2019S and GBA variants with longitudinal cognitive and motor decline in PD.

Design, Setting, And Participants: This longitudinal cohort study of continuous measures in LRRK2 PD, GBA PD, LRRK2/GBA PD, and wild-type idiopathic PD used pooled annual visit data ranging from 2004 to 2019 from the Mount Sinai Beth Israel, Parkinson Disease Biomarker Program, Harvard Biomarkers Study, Ashkenazi Jewish-LRRK2-Consortium, Parkinson Progression Marker Initiative, and SPOT-PD studies. Read More

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Genotype and defects in microtubule-based motility correlate with clinical severity in -associated neurological disorder.

HGG Adv 2021 Apr 30;2(2). Epub 2021 Jan 30.

Department of Pediatrics, Columbia University Irving Medical Center, New York, NY 10032, USA.

KIF1A-associated neurological disorder (KAND) encompasses a group of rare neurodegenerative conditions caused by variants in ,a gene that encodes an anterograde neuronal microtubule (MT) motor protein. Here we characterize the natural history of KAND in 117 individuals using a combination of caregiver or self-reported medical history, a standardized measure of adaptive behavior, clinical records, and neuropathology. We developed a heuristic severity score using a weighted sum of common symptoms to assess disease severity. Read More

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Clinical and genetic analysis of 2 rare cases of Wiskott-Aldrich syndrome from Chinese minorities: Two case reports.

Medicine (Baltimore) 2021 Apr;100(16):e25527

Kunming Key Laboratory of Children Infection and Immunity, Yunnan Key Laboratory of Children's Major Disease Research, Yunnan Medical Center for Pediatric Diseases, Yunnan Institute of Pediatrics.

Rationale: Wiskott-Aldrich syndrome (WAS) is a rare X-linked recessive disease characterized by thrombocytopenia, small platelets, eczema, immunodeficiency, and an increased risk of autoimmunity and malignancies. X-linked thrombocytopenia (XLT), the milder phenotype of WAS, is always limited to thrombocytopenia with absent or slight infections and eczema. Here, we illustrated the clinical and molecular characteristics of 2 unrelated patients with WAS from Chinese minorities. Read More

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Defining the risk profile of women with stage 1 hypertension: A time to event analysis.

Am J Obstet Gynecol MFM 2021 Apr 17:100376. Epub 2021 Apr 17.

Department of Obstetrics and Gynecology, Washington University in St. Louis School of Medicine, St. Louis, MO.

Background: Chronic hypertension complicates up to 5% of pregnancies and is increasing in prevalence. Women with hypertension have increased risks of serious maternal morbidity and mortality in pregnancy including the development of preeclampsia. In 2017, new guidelines reclassified blood pressure into four categories: normal (<120/<80 mmHg), elevated (120-129/<80 mmHg), stage 1 hypertension (130-139/80-89 mmHg), and stage 2 hypertension (>140/>90 mmHg). Read More

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A GDF5 frameshift mutation segregating with Grebe type chondrodysplasia and Brachydactyly Type C+ in a 6 generations family: Clinical report and mini review.

Eur J Med Genet 2021 Apr 16:104226. Epub 2021 Apr 16.

Human Molecular Genetics Laboratory, National Institute for Biotechnology and Genetic Engineering (NIBGE) College, PIEAS, Faisalabad, Pakistan. Electronic address:

Different mutations in the Growth/Differentiation Factor 5 gene (GDF5) have been associated with varying types of skeletal dysplasia, including Grebe type chondrodysplasia (GTC), Hunter-Thompson syndrome, Du Pan Syndrome and Brachydactyly type C (BDC). Heterozygous pathogenic mutations exert milder effects, whereas homozygous mutations are known to manifest more severe phenotypes. In this study, we report a GDF5 frameshift mutation (c. Read More

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Discriminating 'DRESS minor' from 'DRESS major': facial oedema aligns to the severe phenotype.

J Am Acad Dermatol 2021 Apr 16. Epub 2021 Apr 16.

Department of Dermatology, King's College Hospital, Denmark Hill, London, SE5 9RS, U.K.

Background: DRESS is a cutaneous and systemic drug allergy disorder. Patients exist on a severity spectrum with some developing a mild form of the disorder which fails to meet the RegiSCAR diagnostic criteria for DRESS.

Objective: We sought to determine if there were any cutaneous or dermatopathological features which discriminate between the mild form of DRESS ('DRESS minor') and the severe phenotype ('DRESS major'). Read More

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Downregulation of TGR5 (GPBAR1) in biliary epithelial cells contributes to the pathogenesis of sclerosing cholangitis.

J Hepatol 2021 Apr 16. Epub 2021 Apr 16.

Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany.

Background&aims: Primary sclerosing cholangitis (PSC) is characterized by chronic inflammation and progressive fibrosis of the biliary tree. The bile acid receptor TGR5 is found on biliary epithelial cells (BECs), where it promotes secretion, proliferation and tight junction integrity. Thus, we speculated that changes in TGR5-expression in BECs may contribute to PSC pathogenesis. Read More

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Lasting effects of mild embryonic ethanol exposure on voltage-gated ion channels in adult zebrafish brain.

Prog Neuropsychopharmacol Biol Psychiatry 2021 Apr 14;110:110327. Epub 2021 Apr 14.

Department of Psychology, University of Toronto, Mississauga, Ontario, Canada. Electronic address:

The zebrafish is increasingly well utilized in alcohol research, particularly in modeling human fetal alcohol spectrum disorders (FASD). FASD results from alcohol reaching the developing fetus intra utero, a completely preventable yet prevalent and devastating life-long disorder. The hope with animal models, including the zebrafish, is to discover the mechanisms underlying this disease, which may aid treatment and diagnosis. Read More

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Parental mosaicism in de novo neurodevelopmental diseases.

Am J Med Genet A 2021 Apr 14. Epub 2021 Apr 14.

Department of Medical Genetics, Maternal and Child Health Hospital of Hunan Province, Changsha, China.

Neurodevelopmental diseases are increasingly recognized to be caused by "de novo" variants with the expanding use of next-generation sequencing. The apparent de novo variants may actually be low-level hereditary parental mosaic variants, which could increase the recurrence risk of disease by >50% and is thought to be an underappreciated cause of neurodevelopmental diseases. Our study aimed to investigate the frequency of parental mosaicism in "de novo" neurodevelopmental diseases. Read More

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