Ania Koziell
A5079588461- Renal Diseases and Glomerulopathies
- Renal and related cancers
- Chronic Kidney Disease and Diabetes
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Genomics and Rare Diseases
- Ion Transport and Channel Regulation
- Cell Adhesion Molecules Research
- Adolescent and Pediatric Healthcare
- Systemic Lupus Erythematosus Research
- Celiac Disease Research and Management
- Tuberous Sclerosis Complex Research
- Genetic factors in colorectal cancer
- Genetic and Kidney Cyst Diseases
- Platelet Disorders and Treatments
- Autoimmune Bullous Skin Diseases
- Immunodeficiency and Autoimmune Disorders
- Cystic Fibrosis Research Advances
- Complement system in diseases
- Pregnancy and Medication Impact
- Systemic Sclerosis and Related Diseases
- Chronic Lymphocytic Leukemia Research
- Urological Disorders and Treatments
- Biomedical Research and Pathophysiology
- Genomic variations and chromosomal abnormalities
- Pulmonary Hypertension Research and Treatments
King's College London
2014-2024
Guy's and St Thomas' NHS Foundation Trust
2011-2024
Evelina London Children's Healthcare
2014-2024
King's College Hospital
2024
Guy's Hospital
2014-2019
St Thomas' Hospital
2007-2018
University of Bristol
2010
GTx (United States)
2009
University College London
2000-2007
University of Birmingham
1999
Heteroplasmy incidence in mitochondrial DNA In humans, (mtDNA) is predominantly maternally inherited. mtDNA under selection to prevent heteroplasmy—the transmission of multiple genetic variants into the next generation. Wei et al. explored human sequences determine genome structure, selection, and transmission. Whole-genome sequencing revealed that about 45% individuals carry heteroplasmic at levels greater than 1% their total mtDNA. Furthermore, studies more 1500 mother-offspring pairs...
Mutations of the novel renal glomerular genes NPHS1 and NPHS2 encoding nephrin podocin cause two types severe nephrotic syndrome presenting in early life, Finnish type congenital (CNF) a form autosomal recessive familial focal segmental glomerulosclerosis (SRN1), respectively. To investigate mechanisms by which mutations might protein leak, we analysed NPHS1/NPHS2 genotype/phenotype relationships 41 non-Finnish CNF patients, four patients with (onset 0 to 3 months) five possible SRN1 6...
Microalbuminuria is significant both as the earliest stage of diabetic nephropathy and an independent cardiovascular risk factor in nondiabetic subjects, whom it associated with insulin resistance. The link between disorders cellular metabolism albuminuria has been elusive. Here, we report using novel conditionally immortalized human podocytes vitro glomeruli ex vivo that podocyte, principal cell responsible for prevention urinary protein loss, responsive able to approximately double its...
Up to 95% of children presenting with steroid-resistant nephrotic syndrome in early life will have a pathogenic single-gene mutation 1 24 genes currently associated this disease. Others may be affected by polymorphic variants. There is no accepted diagnostic algorithm for clinical genetic testing. The hypothesis was that the increasing reliability next generation sequencing allows comprehensive one-step investigation group and similar patient groups.This study used screen 446 genes,...
Background: Pulmonary arterial hypertension (PAH) is a rare disease with an emerging genetic basis. Heterozygous mutations in the gene encoding bone morphogenetic protein receptor type 2 ( BMPR2 ) are commonest cause of PAH, whereas biallelic eukaryotic translation initiation factor alpha kinase 4 EIF2AK4 described pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Here, we determine frequency these and define genotype-phenotype characteristics large cohort patients...
Of children with idiopathic nephrotic syndrome, 10%-20% fail to respond steroids or develop secondary steroid resistance (termed initial sensitivity) and the majority progress transplantation. Although 30%-50% of these patients suffer disease recurrence after transplantation, poor long-term outcome, no reliable indicator has yet been identified. Notably, incidence transplantation appears reduced in steroid-resistant syndrome (SRNS) due monogenic disorders. We reviewed 150 transplanted SRNS...
Abstract Steroid-resistant nephrotic syndrome (SRNS) causes 15% of chronic kidney disease (CKD). Here we show that recessive mutations in FAT1 cause a distinct renal entity four families with combination SRNS, tubular ectasia, haematuria and facultative neurological involvement. Loss results decreased cell adhesion migration fibroblasts podocytes the is partially reversed by RAC1/CDC42 activator. Podocyte-specific deletion Fat1 mice induces abnormal glomerular filtration barrier development,...
Genetic testing for pathogenic COL4A3–5 variants is usually undertaken to investigate the cause of persistent hematuria, especially with a family history hematuria or kidney function impairment. Alport syndrome experts now advocate genetic even when heterozygous COL4A3 COL4A4 suspected, and cascade their first-degree members because risk impaired function. The recommend too that heterozygotes do not act as donors. Testing in COL4A3–COL4A5 genes should also be performed proteinuria...
Abstract The recent Chandos House meeting of the Alport Variant Collaborative extended indications for screening pathogenic variants in COL4A5, COL4A3 and COL4A4 genes beyond classical phenotype (haematuria, renal failure; family history haematuria or failure) to include persistent proteinuria, steroid-resistant nephrotic syndrome, focal segmental glomerulosclerosis (FSGS), familial IgA glomerulonephritis end-stage kidney failure without an obvious cause. refined ACMG criteria variant...
The leading causes of albuminuria and end-stage renal failure are secondary to abnormalities in the production or cellular action insulin, including diabetes hyperinsulinemic metabolic syndrome. human glomerular podocyte is a critical cell for maintaining filtration barrier kidney preventing albuminuria. We have recently shown this be insulin sensitive with respect glucose uptake, kinetics similar muscle cells. now show that protein nephrin essential process. Conditionally immortalized...
Acute poststreptococcal glomerulonephritis is a common cause of acute nephritis in children. Transient hypocomplementemia and complete recovery are typical, with only minority developing chronic disease. We describe young girl who developed persistent kidney disease after streptococcal throat infection. Kidney biopsy 1 year presentation showed isolated glomerular complement C3 deposition, membranoproliferative changes, subendothelial, intramembranous occasional subepithelial electron-dense...
Steroid–resistant nephrotic syndrome (SRNS), a heterogeneous disorder of the renal glomerular filtration barrier, results in impairment permselectivity. Inheritance genetic SRNS may be autosomal dominant or recessive, with subset recessive presenting as congenital (CNS). Mutations 53 genes are associated human SRNS, but these mutations explain ≤30% patients hereditary cases and only 20% sporadic cases. The proteins encoded by expressed podocytes, malfunction leads to universal end point...
Telomere length is a risk factor in disease and the dynamics of telomere are crucial to our understanding cell replication vitality. The proliferation whole genome sequencing represents an unprecedented opportunity glean new insights into biology on previously unimaginable scale. To this end, number approaches for estimating from whole-genome data have been proposed. Here we present Telomerecat, novel approach estimation length. Previous methods dependent telomeres being known, which may be...
The efficacy of B cell depletion therapies in diseases such as nephrotic syndrome and rheumatoid arthritis suggests a broader role cells human disease than previously recognized. In some these diseases, the minimal change subtype syndrome, pathogenic antibodies immune complexes are not involved. We hypothesized that cells, activated kidney, might produce cytokines capable directly inducing injury proteinuria. To test our hypothesis, we targeted model antigen to kidney glomerulus showed...
The authors applied whole-genome sequencing (WGS) in 9,802 patients with a rare disease national health system to streamline diagnosis and discover unknown aetiological variants the coding non-coding regions of genome. WGS identified genetic 1138/7065 extensively phenotyped participants. They 95 genes which mutations were very likely be cause Mendelian disease.
Background and objectives Intensified immunosuppression in steroid-resistant nephrotic syndrome is broadly applied, with disparate outcomes. This review of patients from the United Kingdom National Study Nephrotic Syndrome cohort aimed to improve disease stratification by determining, comprehensively genetically screened syndrome, if there an association between response initial intensified progression and/or post-transplant recurrence. Design, setting, participants, & measurements...
The influences of vagal and sympathetic efferent activity on sinus arrhythmia in man have been studied healthy subjects by administration hyoscine butylbromide atenolol alone combined using a microcomputer‐linked electrocardiogram (e.c.g.) system. Sinus was quantitated as the S.D. R‐R interval. reduced butylbromide, some to near abolition, but this end‐point unchanged pre‐treatment with atenolol. Atenolol prolonged mean interval increased arrhythmia. It is suggested that mediated through...
Increasing evidence implicates activation of NF-kappaB in a variety glomerular diseases, but the mechanisms involved are unknown. Here, upregulation podocytes transgenic mice resulted glomerulosclerosis and proteinuria. Absence podocyte protein nephrin activation, suggesting that negatively regulates pathway. Signal transduction assays supported functional relationship between suggested involvement atypical kinase C (aPKCzeta/lambda/iota) as an intermediary. We propose disruption slit...
Next-generation sequencing has been invaluable in the elucidation of genetic etiology many subtypes intellectual disability recent years. Here, using exome and whole-genome sequencing, we identified three de novo truncating mutations WAS protein family member 1 (WASF1) five unrelated individuals with moderate to profound autistic features seizures. WASF1, also known as WAVE1, is part WAVE complex acts a mediator between Rac-GTPase actin induce polymerization. The connected by Matchmaker...
Mutations in podocyte and basement membrane genes are associated with a growing spectrum of glomerular disease affecting adults children. Investigation familial cases has helped to build understanding both normal physiology disease. We investigated consanguineous family wide clinical phenotype using clinical, histological, new genetic studies. report striking variability severity nephropathy within an X-linked Alport syndrome (XLAS) family. Four siblings each carried mutant COL4A5 allele,...