Eight-fold increased COVID-19 mortality in autosomal dominant tubulointerstitial kidney disease due to MUC1 mutations: an observational study.

Background: MUC1 and UMOD pathogenic variants cause autosomal dominant tubulointerstitial kidney disease (ADTKD). MUC1 is expressed in kidney, nasal mucosa and respiratory tract, while UMOD is expressed only in kidney. Due to haplo-insufficiency ADTKD-MUC1 patients produce approximately 50% of normal mucin-1.

biobank.cy: the Biobank of Cyprus past, present and future.

The Cyprus Biobank collects biosamples, medical and lifestyle information with the aim of reaching 16,500 Cypriots aged ≥ 18-years, by year 2027, as part of a multitasked EU funded project. Volunteers are both from the general population and from disease cohorts of focused research projects, who amongst others will contribute to canvas the architecture of the Cyprus human genome and study the healthy and morbid anatomy of Cypriots. The Cyprus Biobank is a research infrastructure pillar of the biobank.

Eight-Fold Increased COVID-19 Mortality in Autosomal Dominant Tubulointerstitial Kidney Disease due to Mutations: An Observational Study.

Background: and pathogenic variants cause autosomal dominant tubulointerstitial kidney disease (ADTKD). is expressed in kidney, nasal mucosa and respiratory tract, while is expressed only in kidney. Due to haplo-insufficiency ADTKD- patients produce approximately 50% of normal mucin-1.

Massive Parallel DNA Sequencing of Patients with Inherited Cardiomyopathies in Cyprus and Suggestion of Digenic or Oligogenic Inheritance.

Inherited cardiomyopathies represent a highly heterogeneous group of cardiac diseases. DNA variants in genes expressed in cardiomyocytes cause a diverse spectrum of cardiomyopathies, ultimately leading to heart failure, arrythmias, and sudden cardiac death. We applied massive parallel DNA sequencing using a 72-gene panel for studying inherited cardiomyopathies.

Genome-wide association studies reconstructing chronic kidney disease.

Chronic kidney disease (CKD) is a major health problem with an increasing epidemiological burden, and is the 16th leading cause of years of life lost worldwide. It is estimated that more than 10% of the population have a variable stage of CKD, while about 850 million people worldwide are affected. Nevertheless, public awareness remains low, clinical access is inappropriate in many circumstances and medication is still ineffective due to the lack of clear therapeutic targets.

Genetic Modifiers of Mendelian Monogenic Collagen IV Nephropathies in Humans and Mice.

Familial hematuria is a clinical sign of a genetically heterogeneous group of conditions, accompanied by broad inter- and intrafamilial variable expressivity. The most frequent condition is caused by pathogenic (or likely pathogenic) variants in the collagen-IV genes, . Pathogenic variants in are responsible for the severe X-linked glomerulopathy, Alport syndrome (AS), while homozygous or compound heterozygous variants in the or the gene cause autosomal recessive AS.

Case report: Aborted sudden cardiac death as a first presentation of severe mitral annulus disjunction-a case series and review of the literature.

Mitral annulus disjunction (MAD) is defined as a systolic displacement between the ventricular myocardium and the posterior mitral annulus supporting the posterior mitral leaflet. This structural abnormality is associated with the loss of mechanical annular function manifested as an abnormal systolic excursion of the leaflet hinge point into the left atrium but with maintained electrical function, separating the left atrium and ventricle electrophysiologically. The mitro-aortic fibrous continuity limits MAD anteriorly, between the aortic cusps and the anterior leaflet of the mitral valve.

Genomic Classifiers in Personalized Prostate Cancer Radiation Therapy Approaches: A Systematic Review and Future Perspectives Based on International Consensus.

Current risk-stratification systems for prostate cancer (PCa) do not sufficiently reflect the disease heterogeneity. Genomic classifiers (GC) enable improved risk stratification after surgery, but less data exist for patients treated with definitive radiation therapy (RT) or RT in oligo-/metastatic disease stages. To guide future perspectives of GCs for RT, we conducted (1) a systematic review on the evidence of GCs for patients treated with RT and (2) a survey of experts using the Delphi method, addressing the role of GCs in personalized treatments to identify relevant fields of future clinical and translational research.

A Comparative Presentation of Mouse Models That Recapitulate Most Features of Alport Syndrome.

Alport syndrome is a hereditary kidney disease caused by mutations in the three genes encoding for collagen IV: , and . Several mouse models have been created for the study of this disease with variable phenotypic outcomes. This review is an up-to-date presentation of the current mouse models existing in the literature with a detailed comparison of the phenotypic features characterizing each model.

Dynamic monitoring of PD-L1 and Ki67 in circulating tumor cells of metastatic non-small cell lung cancer patients treated with pembrolizumab.

Programmed cell death protein ligand-1 (PD-L1) expression in non-small cell lung cancer (NSCLC) tumors guides treatment selection. PD-L1 expression in circulating tumor cells (CTCs) may provide further information. We have explored PD-L1 and marker of proliferation Ki-67 (Ki67; also known as MKI67) in CTCs in longitudinal samples of 47 advanced NSCLC patients receiving pembrolizumab.

Germline MBD4 deficiency causes a multi-tumor predisposition syndrome.

We report an autosomal recessive, multi-organ tumor predisposition syndrome, caused by bi-allelic loss-of-function germline variants in the base excision repair (BER) gene MBD4. We identified five individuals with bi-allelic MBD4 variants within four families and these individuals had a personal and/or family history of adenomatous colorectal polyposis, acute myeloid leukemia, and uveal melanoma. MBD4 encodes a glycosylase involved in repair of G:T mismatches resulting from deamination of 5'-methylcytosine.

The 2019 and 2021 International Workshops on Alport Syndrome.

In 1927 Arthur Cecil Alport, a South African physician, described a British family with an inherited form of kidney disease that affected males more severely than females and was sometimes associated with hearing loss. In 1961, the eponymous name Alport syndrome was adopted. In the late twentieth century three genes responsible for the disease were discovered: , , and encoding for the α3, α4, α5 polypeptide chains of type IV collagen, respectively.

Genotype-phenotype correlations for COL4A3-COL4A5 variants resulting in Gly substitutions in Alport syndrome.

Alport syndrome is the commonest inherited kidney disease and nearly half the pathogenic variants in the COL4A3-COL4A5 genes that cause Alport syndrome result in Gly substitutions. This study examined the molecular characteristics of Gly substitutions that determine the severity of clinical features. Pathogenic COL4A5 variants affecting Gly in the Leiden Open Variation Database in males with X-linked Alport syndrome were correlated with age at kidney failure (n = 157) and hearing loss diagnosis (n = 80).

Circulating IgG Levels in SARS-CoV-2 Convalescent Individuals in Cyprus.

Long-term persistence and the heterogeneity of humoral response to SARS-CoV-2 have not yet been thoroughly investigated. The aim of this work is to study the production of circulating immunoglobulin class G (IgG) antibodies against SARS-CoV-2 in individuals with past infection in Cyprus. Individuals of the general population, with or without previous SARS-CoV-2 infection, were invited to visit the Biobank at the Center of Excellence in Biobanking and Biomedical Research of the University of Cyprus.

Guidelines for Genetic Testing and Management of Alport Syndrome.

Genetic testing for pathogenic variants is usually undertaken to investigate the cause of persistent hematuria, especially with a family history of hematuria or kidney function impairment. Alport syndrome experts now advocate genetic testing for persistent hematuria, even when a heterozygous pathogenic or is suspected, and cascade testing of their first-degree family members because of their risk of impaired kidney function. The experts recommend too that or heterozygotes do not act as kidney donors.

Integration of Biobanks in National eHealth Ecosystems Facilitating Long-Term Longitudinal Clinical-Omics Studies and Citizens' Engagement in Research Through eHealthBioR.

Biobanks have long existed to support research activities with BBMRI-ERIC formed as a European research infrastructure supporting the coordination for biobanking with 20 country members and one international organization. Although the benefits of biobanks to the research community are well-established, the direct benefit to citizens is limited to the generic benefit of promoting future research. Furthermore, the advent of General Data Protection Regulation (GDPR) legislation raised a series of challenges for scientific research especially related to biobanking associate activities and longitudinal research studies.

A glycine substitution in the collagenous domain of Col4a3 in mice recapitulates late onset Alport syndrome.

Alport syndrome (AS) is a severe inherited glomerulopathy caused by mutations in the genes encoding the α-chains of type-IV collagen, the most abundant component of the extracellular glomerular basement membrane (GBM). Currently most AS mouse models are knockout models for one of the collagen-IV genes. In contrast, about half of AS patients have missense mutations, with single aminoacid substitutions of glycine being the most common.

Prevalence of clinical, pathological and molecular features of glomerular basement membrane nephropathy caused by or mutations: a systematic review.

Background: Patients heterozygous for or mutations show a wide spectrum of disease, extending from familial isolated microscopic haematuria, as a result of thin basement membranes (TBMs), to autosomal dominant Alport syndrome (ADAS) and end-stage renal disease (ESRD). Many patients are mentioned in the literature under the descriptive diagnosis of TBM nephropathy (TBMN), in which case it actually describes a histological finding that represents the carriers of autosomal recessive Alport syndrome (ARAS), a severe glomerulopathy, as most patients reach ESRD at a mean age of 25 years.

Methods: We performed a systematic literature review for patients with heterozygous / mutations with the aim of recording the spectrum and frequency of pathological features.

Mild X-linked Alport syndrome due to the COL4A5 G624D variant originating in the Middle Ages is predominant in Central/East Europe and causes kidney failure in midlife.

A study of 269 children enrolled into a National Registry for children with persistent glomerular hematuria identified 131 individuals with genetically confirmed X-linked Alport Syndrome. A single variant c.1871G>A p.