ABSTRACT
OBJECTIVES: For the first time we used targeted next-generation sequencing to detect candidate pathogenic variants in Slovak cardiomyopathy patients. BACKGROUND: Targeted next-generation sequencing is considered to be the best practice in genetic diagnostics of cardiomyopathies. However, in Slovakia, with high cardiomyopathies prevalence of 1/440, the current diagnostic tests are still based on Sanger sequencing of a few genes. Consequently, little is known about the exact contribution of pathogenic variants in known cardiomyopathy genes in Slovak patients. METHODS: We used a panel of 46 known cardiomyopathy-associated genes to detect genetic variants in 16 Slovak cardiomyopathy patients (6 dilated, 8 hypertrophic, 2 non-compaction subtypes). RESULTS: We identified candidate pathogenic variants in 11 of 16 patients (69 %). Genes with higher count of candidate pathogenic variants were MYBPC3, MYH and TTN, each with 3 different variants. Seven variants ACTC1 (c.329C>T), ANKRD1 (c.683G>T), MYH7 (c.1025C>T), PKP2 (c.2003delA), TTN (c.51655C>T, c.84841G>T, c.101874_101881delAGAATTTG) have been detected for the first time and might represent Slovak-specific genetic cause. CONCLUSIONS: We have performed genetic testing of previously untested Slovak cardiomyopathy patients using next-generation sequencing cardiomyopathy gene panel. Given the high percentage of candidate pathogenic variants it should be recommended to implement this method into routine genetic diagnostic practice in Slovakia (Tab. 4, Ref. 39).
Subject(s)
Cardiomyopathies , Cardiomyopathy, Hypertrophic , High-Throughput Nucleotide Sequencing , Cardiomyopathies/diagnosis , Cardiomyopathies/drug therapy , Cardiomyopathies/genetics , Cardiomyopathy, Hypertrophic/diagnosis , Cardiomyopathy, Hypertrophic/drug therapy , Cardiomyopathy, Hypertrophic/genetics , Genetic Testing , Humans , SlovakiaABSTRACT
Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS) and genitopatellar syndrome (GTPTS) are clinically similar disorders with some overlapping features. Although they are currently considered to be distinct clinical entities, both were found to be caused by de novo truncating sequence variants in the KAT6B (lysine acetyltransferase 6B) gene, strongly suggesting that they are allelic disorders. Herein, we report the clinical and genetic findings in a girl presenting with a serious multiple congenital anomaly syndrome with phenotypic features overlapping both SBBYSS and GTPTS; pointing out that the clinical distinction between these disorders is not exact and there do exist patients, in whom conventional clinical classification is problematic. Genetic analyses revealed a truncating c.4592delA (p.Asn1531Thrfs*18) variant in the last KAT6B exon. Our findings support that phenotypes associated with typical KAT6B disease-causing variants should be referred to as 'KAT6B spectrum disorders' or 'KAT6B related disorders', rather than their current SBBYSS and GTPTS classification.
Subject(s)
Abnormalities, Multiple/diagnosis , Blepharophimosis/diagnosis , Congenital Hypothyroidism/diagnosis , Craniofacial Abnormalities/diagnosis , Heart Defects, Congenital/diagnosis , Histone Acetyltransferases/genetics , Intellectual Disability/diagnosis , Joint Instability/diagnosis , Kidney/abnormalities , Patella/abnormalities , Psychomotor Disorders/diagnosis , Scrotum/abnormalities , Urogenital Abnormalities/diagnosis , Abnormalities, Multiple/genetics , Abnormalities, Multiple/pathology , Blepharophimosis/genetics , Blepharophimosis/pathology , Child, Preschool , Congenital Hypothyroidism/genetics , Congenital Hypothyroidism/pathology , Craniofacial Abnormalities/genetics , Craniofacial Abnormalities/pathology , Exons , Facies , Female , Heart Defects, Congenital/genetics , Heart Defects, Congenital/pathology , Humans , Intellectual Disability/genetics , Intellectual Disability/pathology , Joint Instability/genetics , Joint Instability/pathology , Kidney/pathology , Mutation , Patella/pathology , Phenotype , Psychomotor Disorders/genetics , Psychomotor Disorders/pathology , Scrotum/pathology , Urogenital Abnormalities/genetics , Urogenital Abnormalities/pathologyABSTRACT
By promoting the inflammatory process in the arterial wall, Chlamydia pneumoniae (CPN) and human cytomegalovirus (CMV) participate in the pathogenesis of cardiovascular disease (CVD). Since patients with diabetes mellitus (DM) are at high risk of CVD, we studied markers of CMV and CPN infection in DM patients as possible predictors of cardiovascular complications. The seroprevalence rates of CMV in 44 DM patients and matched controls were 74 and 88%, respectively. Compared with controls, patients showed lower titers of IgG against CMV (p < 0.001) and higher titers of genus-specific IgA against CPN (p = 0.006). The titers of genus-specific IgG and prevalence rates of type-specific anti-CPN IgA, IgG or IgM were similar in both DM patients and controls. Serological markers of either active or recent CPN infection were detected in 54% of patients and 59% of controls. However, CPN DNA was not detected in the blood of any DM patient. CMV DNA was found in the blood of 1 (2.3%) patient. The results do not indicate an increased rate of CMV or CPN infection in patients with type II DM.
