Rare host variants in ciliary expressed genes contribute to COVID-19 severity in Bulgarian patients.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a pneumonia with extremely heterogeneous clinical presentation, ranging from asymptomatic to severely ill patients. Previous studies have reported links between the presence of host genetic variants and the outcome of the COVID-19 infection. In our study, we used whole exome sequencing in a cohort of 444 SARS-CoV-2 patients, admitted to hospital in the period October-2020-April-2022, to search for associations between rare pathogenic/potentially pathogenic variants and COVID-19 progression.

Clinical and genetic variability among Bulgarian patients with autosomal recessive spastic ataxia of Charlevoix-Saguenay.

Background: Autosomal recessive spastic ataxia ofCharlevoix-Saguenay (ARSACS) is a rare neurodegenerative disorder characterizedby early-onset cerebellar ataxia, peripheral sensorimotor neuropathy, and lowerlimb spasticity. We present clinical andgenetic data of the first Bulgarian patients diagnosed with ARSACS by wholeexome sequencing (WES).

Methods: Variant filtering was performed usinglocally established pipeline and the selected variants were analysed by Sangersequencing.

Introducing Exome Sequencing as Part of the Diagnostic Algorithm for Pediatric Nephrology Patients in Bulgaria: A Single-Center Experience.

Introduction: In pediatric kidney patients, where clinical presentation is often not fully developed, and renal biopsy is too risky or inconclusive, it may be difficult to establish the underlying pathology. In cases such as these, genetic diagnosis may be used to guide treatment, prognosis, and counseling. Given the large number of genes involved in kidney disease, introducing next-generation sequencing with extended gene panels as part of the diagnostic algorithm presents a viable solution.

Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction.

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.

Human cytomegalovirus DNA detection in a recurrent glioblastoma multiforme tumour, but not in whole blood: a case report and discussion about the HCMV latency and therapy perspectives.

In the current study, a 58-year-old male patient presented with recurrent glioblastoma multiforme (GBM). The patient underwent surgical resection, 4 months earlier, followed by radiotherapy and chemotherapy. During the second surgical intervention, tumour tissue and whole blood were sampled and analysed for human cytomegalovirus (HCMV) DNA, immediate early (IE) mRNA and pp65 mRNA.

A Genetic Risk Score to Personalize Prostate Cancer Screening, Applied to Population Data.

Background: A polygenic hazard score (PHS), the weighted sum of 54 SNP genotypes, was previously validated for association with clinically significant prostate cancer and for improved prostate cancer screening accuracy. Here, we assess the potential impact of PHS-informed screening.

Methods: United Kingdom population incidence data (Cancer Research United Kingdom) and data from the Cluster Randomized Trial of PSA Testing for Prostate Cancer were combined to estimate age-specific clinically significant prostate cancer incidence (Gleason score ≥7, stage T3-T4, PSA ≥10, or nodal/distant metastases).

The effect of sample size on polygenic hazard models for prostate cancer.

We determined the effect of sample size on performance of polygenic hazard score (PHS) models in prostate cancer. Age and genotypes were obtained for 40,861 men from the PRACTICAL consortium. The dataset included 201,590 SNPs per subject, and was split into training and testing sets.

Author Correction: Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci.

In the version of this article initially published, the name of author Manuela Gago-Dominguez was misspelled as Manuela Gago Dominguez. The error has been corrected in the HTML and PDF version of the article.

The Role of CD247 Polymorphisms in Bulgarian Patients with Systemic Lupus Erythematosus.

Decreased expression of the TCR ζ-chain has been reported in several autoimmune and inflammatory diseases. Recent evidence suggests that this deficiency may be due to polymorphisms in the CD247 gene. A total 52 patients with systemic lupus erythematosus (SLE) and 95 healthy controls of Bulgarian ethnicity were genotyped for 837C>G, rs1052230, 844A>T, and rs1052231 using a TaqMan genotyping assay.

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants.

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis.

Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci.

Genome-wide association studies (GWAS) and fine-mapping efforts to date have identified more than 100 prostate cancer (PrCa)-susceptibility loci. We meta-analyzed genotype data from a custom high-density array of 46,939 PrCa cases and 27,910 controls of European ancestry with previously genotyped data of 32,255 PrCa cases and 33,202 controls of European ancestry. Our analysis identified 62 novel loci associated (P < 5.

Height, selected genetic markers and prostate cancer risk: results from the PRACTICAL consortium.

This corrects the article DOI: 10.1038/bjc.2017.

Polygenic hazard score to guide screening for aggressive prostate cancer: development and validation in large scale cohorts.

Objectives: To develop and validate a genetic tool to predict age of onset of aggressive prostate cancer (PCa) and to guide decisions of who to screen and at what age.

Design: Analysis of genotype, PCa status, and age to select single nucleotide polymorphisms (SNPs) associated with diagnosis. These polymorphisms were incorporated into a survival analysis to estimate their effects on age at diagnosis of aggressive PCa (that is, not eligible for surveillance according to National Comprehensive Cancer Network guidelines; any of Gleason score ≥7, stage T3-T4, PSA (prostate specific antigen) concentration ≥10 ng/L, nodal metastasis, distant metastasis).

Three novel SLC2A1 mutations in Bulgarian patients with different forms of genetic generalized epilepsy reflecting the clinical and genetic diversity of GLUT1-deficiency syndrome.

Purpose: GLUT1-deficiency syndrome (GLUT1-DS) is a metabolic brain disorder with a great clinical heterogeneity underlined by various mutations in the SLC2A1 gene which make the clinical and genetic diagnosis complicated. The purpose of our study is to investigate the genetic defects affecting the SLC2A1 gene in a group of Bulgarian patients with genetic generalized epilepsy (GGE), and to bring new insights into the molecular pathology of GLUT1-DS that would strengthen the genotype-phenotype correlations and improve the diagnostic procedure.

Methods: We have performed sequencing analysis of the SLC2A1 gene in thirty-eight Bulgarian patients with different forms of GGE having emerged in childhood followed by array comparative genome (aCGH) hybridization in patients with severe forms of GLUT1-DS who display extraneurological features.

Height, selected genetic markers and prostate cancer risk: results from the PRACTICAL consortium.

Background: Evidence on height and prostate cancer risk is mixed, however, recent studies with large data sets support a possible role for its association with the risk of aggressive prostate cancer.

Methods: We analysed data from the PRACTICAL consortium consisting of 6207 prostate cancer cases and 6016 controls and a subset of high grade cases (2480 cases). We explored height, polymorphisms in genes related to growth processes as main effects and their possible interactions.

A familial case of severe infantile nephronophthisis explained by oligogenic inheritance.

Renal cysts are common malformation during the prenatal and postnatal period and frequent cause of chronic kidney or ESRD. More than 70 genes have been shown to play role in their pathology. Part of them are responsible for the structure and function of the cilia, which assigns a large proportion of the renal cystic diseases in the ciliopathies.

HPLC-UV and LC-MS Analyses of Acylquinic Acids in Geigeria alata (DC) Oliv. & Hiern. and their Contribution to Antioxidant and Antimicrobial Capacity.

Introduction: Geigeria alata is a traditional plant used in Sudanese folk medicine for treatment of diabetes, cough, epilepsy and intestinal complaints.

Objective: To analyze phenolic acids in Geigeria alata roots and leaves and to evaluate their antioxidant and antimicrobial activities.

Methodology: Phenolic acids in the aqueous-methanol extracts were identified by LC-MS.

Polymorphisms in androgen metabolism genes AR, CYP1B1, CYP19, and SRD5A2and prostate cancer risk and aggressiveness in Bulgarian patients.

Background/aim: The aim of our study was to elucidate the role of polymorphisms in AR, CYP1B1, CYP19, and SRD5A2 genes for prostate cancer (PC) development in Bulgarian patients.

Materials And Methods: We genotyped 246 PC patients and 261 controls (155 with benign prostate hyperplasia and 107 healthy population controls) using direct sequencing, PCR-RFLP, SSCP, and fragment analysis.

Results: The allele and genotype frequencies of most of the studied variants did not differ significantly between cases and controls.

Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types.

Unlabelled: Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis, but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P < 10(-8) seven new cross-cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type.

Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation.

Although genome-wide association studies have identified over 100 risk loci that explain ∼33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines.

Steroid-resistant nephrotic syndrome caused by novel WT1 mutation inherited from a mosaic parent.

Steroid-resistant nephrotic syndrome (SRNS) is a severe childhood disorder frequently progressing toward renal failure. Among its genetic causes are mutations in the Wilms tumor gene, WT1, which codes for a transcription factor with key role for the embryonic development of the genitourinary tract as well as for maintaining podocyte differentiation and slit diaphragm structure in adults. Defects in WT1 are associated with sporadic cases of both syndromic and isolated SRNS.