Objective: The explanation of the genetic aspects of dilatative cardiomyopathy (DCM) is important... more Objective: The explanation of the genetic aspects of dilatative cardiomyopathy (DCM) is important for at least two major reasons: 1. there is a phenotypic and clinical overlap between the various cardiomyopathies with DCM - thus it might be suggested DCM may be an end phenotype; 2. genetic predisposition to DCM might render the myocardium susceptible to various exogenous factors such as infections, alcohol, toxins, etc. Design and method: We share the results from the Next Gene sequencing of 10 patients with DCM. They were of various ages, with the inclusion requirement to be without coronary or hypertensive disease, and clinical manifestations of the DCM from yearly age. Bioinformatics analysis of the data was done with the appropriate protocol on a Dragen server, as well as VarSeq (Goldenhelix) for all NGS data. Results: This case series of Caucasian patients with DCM presented with mutations in TTN, TTN-AS1, SCN5A, RYR2, DSG2, DSG2-AS1, FLNC, LAMA4, ACTN2, GATA6, DMD genes. All t...
Objective The aim of this study was to investigate the potential association of rs11206510 in PCS... more Objective The aim of this study was to investigate the potential association of rs11206510 in PCSK9 gene with coronary artery disease (CAD) and myocardial infarction (MI) in Bulgarians. Materials and Methods The current analysis included 261 patients with angiographically documented CAD (153 with MI and 108 without MI) and 496 population – based controls. Genomic DNA was extracted from venous blood samples. The selected polymorphism was genotyped by TaqMan SNP Genotyping Assay. The genotype and allele frequencies were compared between cases and controls using χ2 test. Results In this study, the presence of the T allele of rs11206510 in the PCSK9 gene was found to be associated with elevated risk for MI in patients with already existing myocardial ischemia (allele T, OR1.78,CI95:1.16-2.73, p = 0.007). The result was enhanced in the male subgroup (allele T, OR1.74, CI95:1.02-2.96, p = 0.038). Also, we found reduced risk of CAD (without MI) for T allele (OR0.70, CI95:0.49-0.99, p = 0.0...
Journal of IMAB - Annual Proceeding (Scientific Papers)
Purpose: This pilot study was designed to investigate the impact of a moderate-calorie Mediterran... more Purpose: This pilot study was designed to investigate the impact of a moderate-calorie Mediterranean diet compared to a regular diet with omega-3 PUFAs (eicosapentaenoic and docosahexaenoic acids) supplementation on fatigue symptoms in patients with relapsing-remitting multiple sclerosis (RRMS) and to assess the optional benefit of the diet on their quality of life. Material/Methods: This 12-month pilot study was conducted in 2021 at the Department of Neurology, Medical University – Pleven, Bulgaria. A total of 60 patients with RRMS aged 18-64 were selected from the database of the Neurology Clinic at the University Hospital "Dr Georgi Stranski" – Pleven. From the selected patients, only 30 were included in the pilot phase and respectively assigned to the nutritional arms. Blood samples were collected twice – at the first and second visit in 3 months, for metabolic and dietary parameters analysis. Symptoms of fatigue were assessed with Fatigue Scale for Motor and Cognitive...
R. TZVEOVA1, T. YANEVA3, G. DIMITROV3, D. PENDICHEVA-DUHLENSKA5, S. VANDEVA4, Y. MATROZOVA4, K. N... more R. TZVEOVA1, T. YANEVA3, G. DIMITROV3, D. PENDICHEVA-DUHLENSKA5, S. VANDEVA4, Y. MATROZOVA4, K. NAYDENOV2, O. BELTCHEVA1, AT. MITKOVA1, S. ZACHARIEVA4, R. TURNOVSKA-KADREVA3, G. NACHEV6, V. MITEV1 AND R. KANEVA1 1Molecular Medicine Center, Department of Medical Chemistry and Biochemistry, Medical University – So a 2Department of Medical Chemistry and Biochemistry, Medical University – So a 3Clinic of Cardiology, University Hospital “Aleksandrovska” – So a 4Clinical Center of Endocrinology and Gerontology, Medical University – So a 5Department of Experimental and Clinical Pharmacology, Dermatology and Venereology, Medical University – Pleven 6National University Specialized Hospital for Active Treatment “Sv. Ekaterina” – So a
Objective: To investigate for the first time in the South-Eastern population the possible associa... more Objective: To investigate for the first time in the South-Eastern population the possible association of seven polymorphic variants from genome-wide association studies (GWASs) with essential hypertension (EH): rs890283, rs2229238, rs1173771, rs9349379, rs3918226, rs2681472, rs579459, in or near the genes CYP2J2, IL6R, NPR3 - C5orf23, PHACTR1, eNOS, ATP2B1, ABO, respectively, and to further explore the epistasis interactions that are involved in the pathophysiology of high blood pressure. Design and method: 794 Bulgarian subjects were included: 496 normotensive (population controls) and 298 hypertensive. Genomic DNA was extracted from venous blood samples. Chemagic Magnetic Separation Module I was used to prepare the isolation step. All variants were genotyped with TaqMan Allelic Discrimination Assays and the epistasis interaction was analyzed. We used &khgr;2 test and generalized multifactor dimensionality reduction (GMDR) analysis to identify the models of genotype interaction. Da...
R. TZVEOVA1, 2, T. YANEVA3, G. DIMITROV3, D. PENDICHEVA-DUHLENSKA5, S. VANDEVA4, Y. MATROZOVA4, K... more R. TZVEOVA1, 2, T. YANEVA3, G. DIMITROV3, D. PENDICHEVA-DUHLENSKA5, S. VANDEVA4, Y. MATROZOVA4, K. NAYDENOV2, O. BELTCHEVA1, 2, A. MITKOVA1, 2, S. ZACHARIEVA4, R. TURNOVSKA-KADREVA3, G. NACHEV4, V. MITEV1, 2 AND R. KANEVA1, 2 1Molecular Medicine Center, Medical University – So a 2Department of Medical Chemistry and Biochemistry, Medical University – So a 3Clinic of Cardiology, University Hospital “Aleksandrovska” – So a 4Clinical Center of Endocrinology and Gerontology, Medical University – So a 5Department of Experimental and Clinical Pharmacology, Dermatology and Venereology, Medical University – Pleven 6University National Specialized Hospital for Active Treatment Hospital “Sv. Ekaterina” – So a
We studied carotid radial PWV in 881 subjects, 564 hypertensives aged 60 ± 12.5 years old (281 me... more We studied carotid radial PWV in 881 subjects, 564 hypertensives aged 60 ± 12.5 years old (281 men aged 58.4 ± 12.8 years old & 283 women aged 61.5 ± 12.1 years old), 142 diabetic-hypertensives aged 62.9 ± 10.9 years old (74 men aged 63.3 ± 10.4 years old and 68 women aged 62.4 ± 11 years old) and 175 healthy subjects aged 54.7 ± 14.3 years old (61 men aged 49.2 ± 15.7 & 114 women aged 57.6 ± 12.9 years old) by means of Complior ® before and after 3 min of brachial ischemia induced by sphygmomanometer cuff compression Results: Healthy people reduced PWV 10.8% (p < 0.0001) (-8.0% among men and -14.1% among women) meanwhile hypertensives reduced 3.1% (-4.1% among men and -2.1% among women) and in hypertensive diabetics variation was -1.9% (-3.4% among men and -0.4 among women)
Objective: To determine the relationship between blood pressure (BP), lipid metabolism and levels... more Objective: To determine the relationship between blood pressure (BP), lipid metabolism and levels of IL-1beta and IL-6 in patients with type 2 diabetes mellitus (T2DM). A total of 96 patients with T2DM (mean age 52.74 ± 9.56, 38 women) and 20 healthy volunteers were examined. A systolic blood pressure (SBP, mmHg), diastolic blood pressure (DBP, mmHg), and mean arterial pressure (MAP) were measured; levels of total cholesterol (TC), high density lipoprotein cholesterol (HDL), triglycerides (TG) were determined by biochemical method (mmol/L), the level of low density lipoprotein cholesterol (LDL) was calculated by Friedwald's formula. The levels of IL-1-beta and IL-6 were determined by ELISA (ng/ml).
To investigate the expression and potential target of micro-92b (miR-92b) in angiotensin II (Ang-... more To investigate the expression and potential target of micro-92b (miR-92b) in angiotensin II (Ang-II)-induced mouse cardiac hypertrophy. We established mouse cardiac hypertrophy models of Ang-II infusion and pressure-overloading by transverse aortic constriction (TAC). To investigate the effect of miR-92b on Ang-II-induced hypertrophy in vivo, 24 C57BL/6 mice were randomized into 4 groups: (1) agomiR-negative control (NC) + saline, (2) agomiR-NC + Ang-II (NC agomir with Ang-II infusion), (3) agomiR-92 + saline (miR-92b agomir with saline infusion), and (4) agomiR-92+ Ang-II (miR-92b agomir with Ang-II infusion).Left ventricular (LV) function variables were assessed by transthoracic echocardiography.Wheat germ agglutinin (WGA) staining was performed on mouse ventricular myocardium. Neonatal mouse ventricular cells (NMVCs) were isolated from the hearts of 1-3-d-old newborn C57BL6 mice. FITC-phalloidin staining was used on cultured NMVCs. The expression of miR-92b and hypertrophic gene mRNA were measured by Reversetranscription quantitative PCR. The expression of protein were determined by western blot analysis. Dual luciferase assay was for HAND2 target identifi cation. Results: miR-92b signifi cantly decreases in hypertrophic myocardium and cardiomyocytes. Over-expression of miR-92b can result in a reduction of the expression of genes related to myocardial hypertrophy and ameliorate the angiotensin II (Ang-II) -induced cardiac hypertrophy in mice. Our date shows that miR-92b negatively regulated Heart and neural crest derivatives-expressed 2 (HAND2) expression by directly targeting the untranslated region (UTR) of HAND2 mRNA. We have also found that both miR-92b mimic and HAND2 siRNA could resultfully inhibit Ang-II-induced hypertrophy in mouse cardiomyocytes. Conclusions: miR-92b modulates HAND2 during myocardial hypertrophy and overexpression of miR-92b performs as a protective factor against myocardial hypertrophy.
Introduction: Transient periosteal hyperostosis with dysproteinemia, also named Goldbloom syndrom... more Introduction: Transient periosteal hyperostosis with dysproteinemia, also named Goldbloom syndrome (GS), is a rare pediatric disease characterized by recurrent crisis of bone pain, fever, increased inflammatory markers and dysproteinemia. From 1966 only few cases have been reported in the English literature. Objectives: To better define the clinical and epidemiological features of GS. Methods: We report clinical, laboratory and radiological features of our patients in Table , comparing with the English literature. Results: Case 1 was a 9-year-old girl who presented daily crisis of bone pain at the lower limbs, associated with fever spikes, limping and nocturnal awakenings. Physical examination was normal. Laboratory tests showed mild anemia, thrombocytosis, increased inflammatory markers and high antibody levels against streptolysine O and DNase-B (ASO 4280 IU/ml and ADN-B 6310 UI/ml, respectively). Throat swab was positive for group A β-hemolytic streptococcus (GAS). Unusual dysproteinemia, characterized by hypoalbuminemia with increased a1, a2 and g globulinemia, was noted. X-ray evaluation of the lower limbs showed increased bone density at femurs and tibias with signs of periostitis: on STIR sequence MRI these bones presented areas of hyperintense signal. Bone biopsy revealed a thickened periosteum that was strongly adherent to the underlying tissue. Histopathologic study showed signs of chronic inflammation. Steroid treatment was started, leading to a prompt resolution of the clinical picture within few days. Case 2 was a 6-years-old girl who developed, two weeks after an untreated febrile pharyngitis, daily attacks of severe pain at ankles with fever. Joint examination was normal. Throat swab was positive for GAS. In the following weeks, recurrent crisis of bone pain persisted with a severe weight loss. She was hospitalized and laboratory tests showed mild anemia, thrombocytosis and unusual dysproteinemia with hypoalbuminemia and high a1, a2 and g globulinemia. Inflammatory markers and antibodies against GAS were elevated (ASO 775 IU/ml, AND-B 1660 U/ml). STIR sequence MRI showed hyperintense areas at the femurs, tibias, humerus and ulnas, associated with a thickened pretibial soft tissue. Bone marrow biopsy showed signs of chronic inflammation. A short cycle of steroids was administered with rapid resolution of symptoms, turning off inflammatory markers. Immaging became normal after three months. Conclusion: Our patients fulfill the GS features with evidence of previous GAS infection. Our patients lived in the same area of Northern Italy and presented the onset of GS a week apart. Our experience suggests that a timely diagnosis and a short cycle of steroid may rapidly change the history of GS.
Background. Breast cancer is the most commonly diagnosed malignancy and the most frequent cause o... more Background. Breast cancer is the most commonly diagnosed malignancy and the most frequent cause of death in women due to cancer. About 5% to 10% of breast cancers are thought to be hereditary. Pathogenic mutations in BRCA1/2 genes across Hereditary Breast and Ovarian Cancer (HBOC) patients estimates are at around 15-20%. Other less common genes have also been associated with an increased risk of developing breast cancer, such as mutations in the TP53, PTEN, RAD51C, CDH1, ATM, CHEK2 or PALB2 tumor suppression genes. NGS based sequencing panels allow fast and simultaneous screening of large number of high- and low-penetrance susceptibility genes in these patients. Methods. In the current study we included a group of 31 Bulgarian female breast cancer patients, selected following the strict BCLC and NCCN criteria for hereditary cancer. All of them were prescreened by direct sequencing and MLPA analysis, and tested negative for pathogenic mutations in BRCA1 and BRCA2 genes. Next generati...
Steroid-resistant nephrotic syndrome (SRNS) is a severe childhood disorder frequently progressing... more 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. We report here a novel WT1 mutation associated with SRNS in a female patient, which leads to a Cys428Ser substitution on protein level, affecting one of the cysteine residues responsible for zinc binding in the second zinc finger domain. Surprisingly, the mutation identified in the patient was found to be inherited from the healthy mosaic mother. The presence of mosaicism was confirmed using quantitative polymerase chain reaction (PCR) high-resolution melting. The clinical implications of this finding for the family are discussed.
Objective: The explanation of the genetic aspects of dilatative cardiomyopathy (DCM) is important... more Objective: The explanation of the genetic aspects of dilatative cardiomyopathy (DCM) is important for at least two major reasons: 1. there is a phenotypic and clinical overlap between the various cardiomyopathies with DCM - thus it might be suggested DCM may be an end phenotype; 2. genetic predisposition to DCM might render the myocardium susceptible to various exogenous factors such as infections, alcohol, toxins, etc. Design and method: We share the results from the Next Gene sequencing of 10 patients with DCM. They were of various ages, with the inclusion requirement to be without coronary or hypertensive disease, and clinical manifestations of the DCM from yearly age. Bioinformatics analysis of the data was done with the appropriate protocol on a Dragen server, as well as VarSeq (Goldenhelix) for all NGS data. Results: This case series of Caucasian patients with DCM presented with mutations in TTN, TTN-AS1, SCN5A, RYR2, DSG2, DSG2-AS1, FLNC, LAMA4, ACTN2, GATA6, DMD genes. All t...
Objective The aim of this study was to investigate the potential association of rs11206510 in PCS... more Objective The aim of this study was to investigate the potential association of rs11206510 in PCSK9 gene with coronary artery disease (CAD) and myocardial infarction (MI) in Bulgarians. Materials and Methods The current analysis included 261 patients with angiographically documented CAD (153 with MI and 108 without MI) and 496 population – based controls. Genomic DNA was extracted from venous blood samples. The selected polymorphism was genotyped by TaqMan SNP Genotyping Assay. The genotype and allele frequencies were compared between cases and controls using χ2 test. Results In this study, the presence of the T allele of rs11206510 in the PCSK9 gene was found to be associated with elevated risk for MI in patients with already existing myocardial ischemia (allele T, OR1.78,CI95:1.16-2.73, p = 0.007). The result was enhanced in the male subgroup (allele T, OR1.74, CI95:1.02-2.96, p = 0.038). Also, we found reduced risk of CAD (without MI) for T allele (OR0.70, CI95:0.49-0.99, p = 0.0...
Journal of IMAB - Annual Proceeding (Scientific Papers)
Purpose: This pilot study was designed to investigate the impact of a moderate-calorie Mediterran... more Purpose: This pilot study was designed to investigate the impact of a moderate-calorie Mediterranean diet compared to a regular diet with omega-3 PUFAs (eicosapentaenoic and docosahexaenoic acids) supplementation on fatigue symptoms in patients with relapsing-remitting multiple sclerosis (RRMS) and to assess the optional benefit of the diet on their quality of life. Material/Methods: This 12-month pilot study was conducted in 2021 at the Department of Neurology, Medical University – Pleven, Bulgaria. A total of 60 patients with RRMS aged 18-64 were selected from the database of the Neurology Clinic at the University Hospital "Dr Georgi Stranski" – Pleven. From the selected patients, only 30 were included in the pilot phase and respectively assigned to the nutritional arms. Blood samples were collected twice – at the first and second visit in 3 months, for metabolic and dietary parameters analysis. Symptoms of fatigue were assessed with Fatigue Scale for Motor and Cognitive...
R. TZVEOVA1, T. YANEVA3, G. DIMITROV3, D. PENDICHEVA-DUHLENSKA5, S. VANDEVA4, Y. MATROZOVA4, K. N... more R. TZVEOVA1, T. YANEVA3, G. DIMITROV3, D. PENDICHEVA-DUHLENSKA5, S. VANDEVA4, Y. MATROZOVA4, K. NAYDENOV2, O. BELTCHEVA1, AT. MITKOVA1, S. ZACHARIEVA4, R. TURNOVSKA-KADREVA3, G. NACHEV6, V. MITEV1 AND R. KANEVA1 1Molecular Medicine Center, Department of Medical Chemistry and Biochemistry, Medical University – So a 2Department of Medical Chemistry and Biochemistry, Medical University – So a 3Clinic of Cardiology, University Hospital “Aleksandrovska” – So a 4Clinical Center of Endocrinology and Gerontology, Medical University – So a 5Department of Experimental and Clinical Pharmacology, Dermatology and Venereology, Medical University – Pleven 6National University Specialized Hospital for Active Treatment “Sv. Ekaterina” – So a
Objective: To investigate for the first time in the South-Eastern population the possible associa... more Objective: To investigate for the first time in the South-Eastern population the possible association of seven polymorphic variants from genome-wide association studies (GWASs) with essential hypertension (EH): rs890283, rs2229238, rs1173771, rs9349379, rs3918226, rs2681472, rs579459, in or near the genes CYP2J2, IL6R, NPR3 - C5orf23, PHACTR1, eNOS, ATP2B1, ABO, respectively, and to further explore the epistasis interactions that are involved in the pathophysiology of high blood pressure. Design and method: 794 Bulgarian subjects were included: 496 normotensive (population controls) and 298 hypertensive. Genomic DNA was extracted from venous blood samples. Chemagic Magnetic Separation Module I was used to prepare the isolation step. All variants were genotyped with TaqMan Allelic Discrimination Assays and the epistasis interaction was analyzed. We used &khgr;2 test and generalized multifactor dimensionality reduction (GMDR) analysis to identify the models of genotype interaction. Da...
R. TZVEOVA1, 2, T. YANEVA3, G. DIMITROV3, D. PENDICHEVA-DUHLENSKA5, S. VANDEVA4, Y. MATROZOVA4, K... more R. TZVEOVA1, 2, T. YANEVA3, G. DIMITROV3, D. PENDICHEVA-DUHLENSKA5, S. VANDEVA4, Y. MATROZOVA4, K. NAYDENOV2, O. BELTCHEVA1, 2, A. MITKOVA1, 2, S. ZACHARIEVA4, R. TURNOVSKA-KADREVA3, G. NACHEV4, V. MITEV1, 2 AND R. KANEVA1, 2 1Molecular Medicine Center, Medical University – So a 2Department of Medical Chemistry and Biochemistry, Medical University – So a 3Clinic of Cardiology, University Hospital “Aleksandrovska” – So a 4Clinical Center of Endocrinology and Gerontology, Medical University – So a 5Department of Experimental and Clinical Pharmacology, Dermatology and Venereology, Medical University – Pleven 6University National Specialized Hospital for Active Treatment Hospital “Sv. Ekaterina” – So a
We studied carotid radial PWV in 881 subjects, 564 hypertensives aged 60 ± 12.5 years old (281 me... more We studied carotid radial PWV in 881 subjects, 564 hypertensives aged 60 ± 12.5 years old (281 men aged 58.4 ± 12.8 years old & 283 women aged 61.5 ± 12.1 years old), 142 diabetic-hypertensives aged 62.9 ± 10.9 years old (74 men aged 63.3 ± 10.4 years old and 68 women aged 62.4 ± 11 years old) and 175 healthy subjects aged 54.7 ± 14.3 years old (61 men aged 49.2 ± 15.7 & 114 women aged 57.6 ± 12.9 years old) by means of Complior ® before and after 3 min of brachial ischemia induced by sphygmomanometer cuff compression Results: Healthy people reduced PWV 10.8% (p < 0.0001) (-8.0% among men and -14.1% among women) meanwhile hypertensives reduced 3.1% (-4.1% among men and -2.1% among women) and in hypertensive diabetics variation was -1.9% (-3.4% among men and -0.4 among women)
Objective: To determine the relationship between blood pressure (BP), lipid metabolism and levels... more Objective: To determine the relationship between blood pressure (BP), lipid metabolism and levels of IL-1beta and IL-6 in patients with type 2 diabetes mellitus (T2DM). A total of 96 patients with T2DM (mean age 52.74 ± 9.56, 38 women) and 20 healthy volunteers were examined. A systolic blood pressure (SBP, mmHg), diastolic blood pressure (DBP, mmHg), and mean arterial pressure (MAP) were measured; levels of total cholesterol (TC), high density lipoprotein cholesterol (HDL), triglycerides (TG) were determined by biochemical method (mmol/L), the level of low density lipoprotein cholesterol (LDL) was calculated by Friedwald's formula. The levels of IL-1-beta and IL-6 were determined by ELISA (ng/ml).
To investigate the expression and potential target of micro-92b (miR-92b) in angiotensin II (Ang-... more To investigate the expression and potential target of micro-92b (miR-92b) in angiotensin II (Ang-II)-induced mouse cardiac hypertrophy. We established mouse cardiac hypertrophy models of Ang-II infusion and pressure-overloading by transverse aortic constriction (TAC). To investigate the effect of miR-92b on Ang-II-induced hypertrophy in vivo, 24 C57BL/6 mice were randomized into 4 groups: (1) agomiR-negative control (NC) + saline, (2) agomiR-NC + Ang-II (NC agomir with Ang-II infusion), (3) agomiR-92 + saline (miR-92b agomir with saline infusion), and (4) agomiR-92+ Ang-II (miR-92b agomir with Ang-II infusion).Left ventricular (LV) function variables were assessed by transthoracic echocardiography.Wheat germ agglutinin (WGA) staining was performed on mouse ventricular myocardium. Neonatal mouse ventricular cells (NMVCs) were isolated from the hearts of 1-3-d-old newborn C57BL6 mice. FITC-phalloidin staining was used on cultured NMVCs. The expression of miR-92b and hypertrophic gene mRNA were measured by Reversetranscription quantitative PCR. The expression of protein were determined by western blot analysis. Dual luciferase assay was for HAND2 target identifi cation. Results: miR-92b signifi cantly decreases in hypertrophic myocardium and cardiomyocytes. Over-expression of miR-92b can result in a reduction of the expression of genes related to myocardial hypertrophy and ameliorate the angiotensin II (Ang-II) -induced cardiac hypertrophy in mice. Our date shows that miR-92b negatively regulated Heart and neural crest derivatives-expressed 2 (HAND2) expression by directly targeting the untranslated region (UTR) of HAND2 mRNA. We have also found that both miR-92b mimic and HAND2 siRNA could resultfully inhibit Ang-II-induced hypertrophy in mouse cardiomyocytes. Conclusions: miR-92b modulates HAND2 during myocardial hypertrophy and overexpression of miR-92b performs as a protective factor against myocardial hypertrophy.
Introduction: Transient periosteal hyperostosis with dysproteinemia, also named Goldbloom syndrom... more Introduction: Transient periosteal hyperostosis with dysproteinemia, also named Goldbloom syndrome (GS), is a rare pediatric disease characterized by recurrent crisis of bone pain, fever, increased inflammatory markers and dysproteinemia. From 1966 only few cases have been reported in the English literature. Objectives: To better define the clinical and epidemiological features of GS. Methods: We report clinical, laboratory and radiological features of our patients in Table , comparing with the English literature. Results: Case 1 was a 9-year-old girl who presented daily crisis of bone pain at the lower limbs, associated with fever spikes, limping and nocturnal awakenings. Physical examination was normal. Laboratory tests showed mild anemia, thrombocytosis, increased inflammatory markers and high antibody levels against streptolysine O and DNase-B (ASO 4280 IU/ml and ADN-B 6310 UI/ml, respectively). Throat swab was positive for group A β-hemolytic streptococcus (GAS). Unusual dysproteinemia, characterized by hypoalbuminemia with increased a1, a2 and g globulinemia, was noted. X-ray evaluation of the lower limbs showed increased bone density at femurs and tibias with signs of periostitis: on STIR sequence MRI these bones presented areas of hyperintense signal. Bone biopsy revealed a thickened periosteum that was strongly adherent to the underlying tissue. Histopathologic study showed signs of chronic inflammation. Steroid treatment was started, leading to a prompt resolution of the clinical picture within few days. Case 2 was a 6-years-old girl who developed, two weeks after an untreated febrile pharyngitis, daily attacks of severe pain at ankles with fever. Joint examination was normal. Throat swab was positive for GAS. In the following weeks, recurrent crisis of bone pain persisted with a severe weight loss. She was hospitalized and laboratory tests showed mild anemia, thrombocytosis and unusual dysproteinemia with hypoalbuminemia and high a1, a2 and g globulinemia. Inflammatory markers and antibodies against GAS were elevated (ASO 775 IU/ml, AND-B 1660 U/ml). STIR sequence MRI showed hyperintense areas at the femurs, tibias, humerus and ulnas, associated with a thickened pretibial soft tissue. Bone marrow biopsy showed signs of chronic inflammation. A short cycle of steroids was administered with rapid resolution of symptoms, turning off inflammatory markers. Immaging became normal after three months. Conclusion: Our patients fulfill the GS features with evidence of previous GAS infection. Our patients lived in the same area of Northern Italy and presented the onset of GS a week apart. Our experience suggests that a timely diagnosis and a short cycle of steroid may rapidly change the history of GS.
Background. Breast cancer is the most commonly diagnosed malignancy and the most frequent cause o... more Background. Breast cancer is the most commonly diagnosed malignancy and the most frequent cause of death in women due to cancer. About 5% to 10% of breast cancers are thought to be hereditary. Pathogenic mutations in BRCA1/2 genes across Hereditary Breast and Ovarian Cancer (HBOC) patients estimates are at around 15-20%. Other less common genes have also been associated with an increased risk of developing breast cancer, such as mutations in the TP53, PTEN, RAD51C, CDH1, ATM, CHEK2 or PALB2 tumor suppression genes. NGS based sequencing panels allow fast and simultaneous screening of large number of high- and low-penetrance susceptibility genes in these patients. Methods. In the current study we included a group of 31 Bulgarian female breast cancer patients, selected following the strict BCLC and NCCN criteria for hereditary cancer. All of them were prescreened by direct sequencing and MLPA analysis, and tested negative for pathogenic mutations in BRCA1 and BRCA2 genes. Next generati...
Steroid-resistant nephrotic syndrome (SRNS) is a severe childhood disorder frequently progressing... more 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. We report here a novel WT1 mutation associated with SRNS in a female patient, which leads to a Cys428Ser substitution on protein level, affecting one of the cysteine residues responsible for zinc binding in the second zinc finger domain. Surprisingly, the mutation identified in the patient was found to be inherited from the healthy mosaic mother. The presence of mosaicism was confirmed using quantitative polymerase chain reaction (PCR) high-resolution melting. The clinical implications of this finding for the family are discussed.
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Papers by Reni Tzveova