Genotype is associated with left ventricular reverse remodelling and early events in recent-onset dilated cardiomyopathy.

Aims: Recent-onset dilated cardiomyopathy (RODCM) is characterized by heterogeneous aetiology and diverse clinical outcomes, with scarce data on genotype-phenotype correlates. Our aim was to correlate individual RODCM genotypes with left ventricular reverse remodelling (LVRR) and clinical outcomes.

Methods And Results: In this prospective study, a total of 386 Czech RODCM patients with symptom duration ≤6 months underwent genetic counselling and whole-exome sequencing (WES).

Pregnancy in women with dilated cardiomyopathy genetic variants.

Introduction And Objectives: Limited information is available on the safety of pregnancy in patients with genetic dilated cardiomyopathy (DCM) and in carriers of DCM-causing genetic variants without the DCM phenotype. We assessed cardiac, obstetric, and fetal or neonatal outcomes in this group of patients.

Methods: We studied 48 women carrying pathogenic or likely pathogenic DCM-associated variants (30 with DCM and 18 without DCM) who had 83 pregnancies.

Post-mortem genetic testing in sudden cardiac death and genetic screening of relatives at risk: lessons learned from a Czech pilot multidisciplinary study.

Sudden cardiac death (SCD) might have an inherited cardiac condition background. Genetic testing supports post-mortem diagnosis and screening of relatives at risk. Our aim is to determine the feasibility of a Czech national collaboration group and to establish the clinical importance of molecular autopsy and family screening.

Outcomes of a multicenter study of the causes of sudden cardiac death (SCD) in the Czech Republic and primary prevention of cardiac arrest in relatives.

Sudden cardiac death (SCD) in individuals younger than 40 years has a heritable cause in a significant part of the cases. Identification of SCD, post mortem genetic analysis along with the cardiological screening examination in first degree represents an important diagnostic tool for the primary prevention of cardiac arrest in victim´s relatives and requires multicentric and multidisciplinary collaboration. Between 2016 and 2021 the complex cardiogenetic analysis was performed in 115 deaths with post mortem diagnosis of cardiomyopathy, acute aortic dissection and cases without morphological finding explaining the cause of death (sudden arrhythmic death or sudden unexplained death).

Novel Variants in Five Families with Aortic/Arterial Aneurysm and Dissection with Variable Connective Tissue Findings.

Thoracic aortic aneurysm and dissection (TAAD) is a major cause of cardiovascular morbidity and mortality. Loss-of-function variants in , encoding the extracellular matrix crosslinking enzyme lysyl oxidase, have been reported to cause familial TAAD. Using a next-generation TAAD gene panel, we identified five additional probands carrying variants, including two missense variants affecting highly conserved amino acids in the catalytic domain and three truncating variants.

Danon disease is an underdiagnosed cause of advanced heart failure in young female patients: a LAMP2 flow cytometric study.

Aims: Danon disease (DD) is a rare X-linked disorder caused by mutations in the lysosomal-associated membrane protein type 2 gene (LAMP2). DD is difficult to distinguish from other causes of dilated or hypertrophic cardiomyopathy (HCM) in female patients. As DD female patients regularly progress into advanced heart failure (AHF) aged 20-40 years, their early identification is critical to improve patient survival and facilitate genetic counselling.

Pigmentary retinopathy can indicate the presence of pathogenic LAMP2 variants even in somatic mosaic carriers with no additional signs of Danon disease.

Purpose: Danon disease (DD) is a rare X-linked disorder caused by pathogenic variants in LAMP2. DD primarily manifests as a severe cardiomyopathy. An early diagnosis is crucial for patient survival.

Molecular autopsy and sudden cardiac death in the young.

Sudden cardiac death is defined as sudden death due to a confirmed cardiovascular disease or when there is no explanation after medico-legal autopsy and arrhythmogenic, possibly hereditary etiology is presumed. Molecular autopsy should be indicated in all cases of sudden cardiac death due to suspected cardiomyopathy and hereditary arrhythmic syndrome. It should also be considered in thoracic aortic dissection.

Desminopathy: Novel Desmin Variants, a New Cardiac Phenotype, and Further Evidence for Secondary Mitochondrial Dysfunction.

The pleomorphic clinical presentation makes the diagnosis of desminopathy difficult. We aimed to describe the prevalence, phenotypic expression, and mitochondrial function of individuals with putative disease-causing desmin (DES) variants identified in patients with an unexplained etiology of cardiomyopathy. A total of 327 Czech patients underwent whole exome sequencing and detailed phenotyping in probands harboring DES variants.

Alu-mediated Xq24 deletion encompassing CUL4B, LAMP2, ATP1B4, TMEM255A, and ZBTB33 genes causes Danon disease in a female patient.

Cullin 4B (CUL4B), lysosomal-associated membrane protein Type 2 (LAMP2), ATP1B4, TMEM255A, and ZBTB33 are neighboring genes on Xq24. Mutations in CUL4B result in Cabezas syndrome (CS). Male CS patients present with dysmorphic, neuropsychiatric, genitourinary, and endocrine abnormalities.

LAMP2 exon-copy number variations in Danon disease heterozygote female probands: Infrequent or underdetected?

Danon disease (DD) is an X-linked disorder caused by mutations in the lysosomal-associated membrane protein 2 (LAMP2) gene (Xq24). DD is characterized by cognitive deficit, myopathy, and cardiomyopathy in male patients. The phenotype is variable and mitigated in females.

Corrigendum: Candidate Gene Resequencing in a Large Bicuspid Aortic Valve-Associated Thoracic Aortic Aneurysm Cohort: as an Important Contributor.

[This corrects the article on p. 400 in vol. 8, PMID: 28659821.

Candidate Gene Resequencing in a Large Bicuspid Aortic Valve-Associated Thoracic Aortic Aneurysm Cohort: as an Important Contributor.

Bicuspid aortic valve (BAV) is the most common congenital heart defect. Although many BAV patients remain asymptomatic, at least 20% develop thoracic aortic aneurysm (TAA). Historically, BAV-related TAA was considered as a hemodynamic consequence of the valve defect.

Distribution of CFTR mutations in the Czech population: positive impact of integrated clinical and laboratory expertise, detection of novel/de novo alleles and relevance for related/derived populations.

Background: This two decade long study presents a comprehensive overview of the CFTR mutation distribution in a representative cohort of 600 Czech CF patients derived from all regions of the Czech Republic.

Methods: We examined the most common CF-causing mutations using the Elucigene CF-EU2v1™ assay, followed by MLPA, mutation scanning and/or sequencing of the entire CFTR coding region and splice site junctions.

Results: We identified 99.

High positive predictive value of PAPP-A for acute coronary syndrome diagnosis in heparin-naïve patients.

Pregnancy-associated plasma protein-A (PAPP-A) was studied as a marker of acute coronary syndrome (ACS). It has been shown that its levels are increased by heparin administration. Therefore, the aim of our study was to ascertain the diagnostic significance of PAPP-A in heparin-naïve patients and compare it with (TnI).

Influence of concomitant heparin administration on pregnancy-associated plasma protein-A levels in acute coronary syndrome with ST segment elevation.

Introduction: The time course of pregnancy-associated plasma protein-A (PAPP-A) levels was studied at admission, immediately after percutaneous coronary intervention (PCI) and 1, 2, 4, 6, 12, 24 and 48 h after PCI in acute coronary syndrome with ST segment elevation (ACS-STE) to determine the impact of PCI, concomitant clinical complications and heparin administration.

Material And Methods: Pregnancy-associated plasma protein-A serum levels, examined by the Kryptor(TM) system, were studied in 30 heparinized PCI ACS-STE patients, in 10 elective PCIs and 12 coronary angiographies with heparin, and in 5 patients with normal coronary angiogram without heparin.

Results: Heparin caused a high PAPP-A increase in ACS-STE patients, in all patients with heparin without ACS and angiographic signs of significant atherosclerosis.

Fine mapping of autosomal dominant nonsyndromic hearing impairment DFNA21 to chromosome 6p24.1-22.3.

Previously, the DFNA21 locus was positioned telomeric to the DFNA13 locus based on testing of candidate loci. One family member in this region did not carry the at risk haplotype, although he had the same nonspecific midfrequency hearing impairment as other affected family members. Hence, we performed a whole genome linkage scan excluding other regions of the genome and confirming the localization of DFNA21 to 6p22.

QF-PCR examination of parental and meiotic origin of trisomy 21 in Central and Eastern Europe.

Study of parental/meiotic origin of free trisomy 21 in nuclear families from Russia (70 cases), Ukraine (32 cases), and 22 from Germany revealed maternal nondisjunction in 77.3% (Germany), 93.8% (Ukraine), and 91.

Homozygosity mapping of a second gene locus for hereditary combined deficiency of vitamin K-dependent clotting factors to the centromeric region of chromosome 16.

Familial multiple coagulation factor deficiency (FMFD) of factors II, VII, IX, X, protein C, and protein S is a very rare bleeding disorder with autosomal recessive inheritance. The phenotypic presentation is variable with respect to the residual activities of the affected proteins, its response to oral administration of vitamin K, and to the involvement of skeletal abnormalities. The disease may result either from a defective resorption/transport of vitamin K to the liver, or from a mutation in one of the genes encoding gamma-carboxylase or other proteins of the vitamin K cycle.

Premature chromosome condensation in humans associated with microcephaly and mental retardation: a novel autosomal recessive condition.

We report a novel autosomal recessive disorder characterized by premature chromosome condensation in the early G2 phase. It was observed in two siblings, from consanguineous parents, affected with microcephaly, growth retardation, and severe mental retardation. Chromosome analysis showed a high frequency of prophase-like cells (>10%) in lymphocytes, fibroblasts, and lymphoblast cell lines with an otherwise normal karyotype.

Association of human aging with a functional variant of klotho.

Mice deficient in Klotho gene expression exhibit a syndrome resembling premature human aging. To determine whether variation in the human KLOTHO locus contributes to survival, we applied two newly characterized polymorphic microsatellite markers flanking the gene in a population-based association study. In a cohort chosen for its homogeneity, Bohemian Czechs, we demonstrated significant differences in selected marker allele frequencies between newborn and elderly individuals (P < 0.