Genetic Determinants Of Clinical Phenotype In Hypertrophic Cardiomyopathy

Abstract Background Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease that affects approximately one in 500 people. HCM is a recognized genetic disorder most often caused by mutations involving myosin-binding protein C (MYBPC3) and β-myosin heavy chain (MYH7) which are responsible for approximately three-quarters of the identified mutations. Methods As a part of the international multidisciplinary SILICOFCM project (www.silicofcm.eu) the present study evaluated the association between underlying genetic mutations and clinical phenotype in patients with HCM. Only patients with confirmed single pathogenic mutations in either MYBPC3 or MYH7 genes were included in the study and divided into two groups accordingly. The MYBPC3 group was comprised of 48 patients (76%), while the MYH7 group included 15 patients (24%). Each patient underwent clinical examination and echocardiography. Results The most prevalent symptom in patients with MYBPC3 was dyspnea (44%), whereas in patients with MYH7 it was palpitations (33%). The MYBPC3 group had a significantly higher number of patients with a positive family history of HCM (46% vs. 7%; p = 0.014). There was a numerically higher prevalence of atrial fibrillation in the MYH7 group (60% vs. 35%, p = 0.085). Laboratory analyses revealed normal levels of creatinine (85.5 ± 18.3 vs. 81.3 ± 16.4 µmol/l; p = 0.487) and blood urea nitrogen (10.2 ± 15.6 vs. 6.9 ± 3.9 mmol/l; p = 0.472) which were similar in both groups. The systolic anterior motion presence was significantly more frequent in patients carrying MYH7 mutation (33% vs. 10%; p = 0.025), as well as mitral leaflet abnormalities (40% vs. 19%; p = 0.039). Calcifications of mitral annulus were registered only in MYH7 patients (20% vs. 0%; p = 0.001). The difference in diastolic function, i.e. E/e′ ratio between the two groups was also noted (MYBPC3 8.8 ± 3.3, MYH7 13.9 ± 6.9, p = 0.079). Conclusions Major findings of the present study corroborate the notion that MYH7 gene mutation patients are presented with more pronounced disease severity than those with MYBPC3.

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Genetic Determinants Of Clinical Phenotype In Hypertrophic Cardiomyopathy

10.21203/rs.3.rs-36810/v1 ◽

2020 ◽

Author(s):

Lazar Velicki ◽

Djordje G Jakovljevic ◽

Andrej Preveden ◽

Miodrag Golubovic ◽

Marija Bjelobrk ◽

...

Keyword(s):

Hypertrophic Cardiomyopathy ◽

Clinical Phenotype ◽

Genetic Disorder ◽

Positive Family History ◽

Mitral Annulus ◽

Genetic Determinants ◽

Myosin Binding Protein ◽

Number Of Patients ◽

History Of ◽

The Difference

Abstract Background: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease that affects approximately one in 500 people. HCM is a recognized genetic disorder most often caused by mutations involving myosin-binding protein C (MYBPC3) and β-myosin heavy chain (MYH7) which are responsible for approximately three-quarters of the identified mutations.Methods: As a part of the international multidisciplinary SILICOFCM project (www.silicofcm.eu) the present study evaluated the association between underlying genetic mutations and clinical phenotype in patients with HCM. Only patients with confirmed single pathogenic mutations in either MYBPC3 or MYH7 genes were included in the study and divided into two groups accordingly. The MYBPC3 group was comprised of 48 patients (76%), while the MYH7 group included 15 patients (24%). Each patient underwent clinical examination and echocardiography.Results: The most prevalent symptom in patients with MYBPC3 was dyspnea (44%), whereas in patients with MYH7 it was palpitations (33%). The MYBPC3 group had a significantly higher number of patients with a positive family history of HCM (46% vs. 7%; p=0.014). There was a numerically higher prevalence of atrial fibrillation in the MYH7 group (60% vs. 35%, p=0.085). Laboratory analyses revealed normal levels of creatinine (85.5±18.3 vs. 81.3±16.4 µmol/l; p=0.487) and blood urea nitrogen (10.2±15.6 vs. 6.9±3.9 mmol/l; p=0.472) which were similar in both groups. The systolic anterior motion presence was significantly more frequent in patients caring MYH7 mutation (33% vs. 10%; p=0.025), as well as mitral leaflet abnormalities (40% vs. 19%; p=0.039). Calcifications of mitral annulus were registered only in MYH7 patients (20% vs. 0%; p=0.001). The difference in diastolic function, i.e. E/e’ ratio between the two groups was also noted (MYBPC3 8.8±3.3, MYH7 13.9±6.9, p=0.079).Conclusions: Major findings of the present study corroborate the notion that MYH7 gene mutation patients are presented with more pronounced disease severity than those with MYBPC3.

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Genetic Determinants of Clinical Phenotype in Hypertrophic Cardiomyopathy

10.21203/rs.3.rs-36810/v3 ◽

2020 ◽

Author(s):

Lazar Velicki ◽

Djordje G Jakovljevic ◽

Andrej Preveden ◽

Miodrag Golubovic ◽

Marija Bjelobrk ◽

...

Keyword(s):

Hypertrophic Cardiomyopathy ◽

Clinical Phenotype ◽

Genetic Disorder ◽

Positive Family History ◽

Mitral Annulus ◽

Genetic Determinants ◽

Myosin Binding Protein ◽

Number Of Patients ◽

History Of ◽

The Difference

Abstract Background: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease that affects approximately one in 500 people. HCM is a recognized genetic disorder most often caused by mutations involving myosin-binding protein C (MYBPC3) and β-myosin heavy chain (MYH7) which are responsible for approximately three-quarters of the identified mutations.Methods: As a part of the international multidisciplinary SILICOFCM project (www.silicofcm.eu) the present study evaluated the association between underlying genetic mutations and clinical phenotype in patients with HCM. Only patients with confirmed single pathogenic mutations in either MYBPC3 or MYH7 genes were included in the study and divided into two groups accordingly. The MYBPC3 group was comprised of 48 patients (76%), while the MYH7 group included 15 patients (24%). Each patient underwent clinical examination and echocardiography.Results: The most prevalent symptom in patients with MYBPC3 was dyspnea (44%), whereas in patients with MYH7 it was palpitations (33%). The MYBPC3 group had a significantly higher number of patients with a positive family history of HCM (46% vs. 7%; p=0.014). There was a numerically higher prevalence of atrial fibrillation in the MYH7 group (60% vs. 35%, p=0.085). Laboratory analyses revealed normal levels of creatinine (85.5±18.3 vs. 81.3±16.4 µmol/l; p=0.487) and blood urea nitrogen (10.2±15.6 vs. 6.9±3.9 mmol/l; p=0.472) which were similar in both groups. The systolic anterior motion presence was significantly more frequent in patients caring MYH7 mutation (33% vs. 10%; p=0.025), as well as mitral leaflet abnormalities (40% vs. 19%; p=0.039). Calcifications of mitral annulus were registered only in MYH7 patients (20% vs. 0%; p=0.001). The difference in diastolic function, i.e. E/e’ ratio between the two groups was also noted (MYBPC3 8.8±3.3, MYH7 13.9±6.9, p=0.079).Conclusions: Major findings of the present study corroborate the notion that MYH7 gene mutation patients are presented with more pronounced disease severity than those with MYBPC3.

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Genetic Determinants Of Clinical Phenotype In Hypertrophic Cardiomyopathy

10.21203/rs.3.rs-36810/v4 ◽

2020 ◽

Author(s):

Lazar Velicki ◽

Djordje G Jakovljevic ◽

Andrej Preveden ◽

Miodrag Golubovic ◽

Marija Bjelobrk ◽

...

Keyword(s):

Hypertrophic Cardiomyopathy ◽

Clinical Phenotype ◽

Genetic Disorder ◽

Positive Family History ◽

Mitral Annulus ◽

Genetic Determinants ◽

Myosin Binding Protein ◽

Number Of Patients ◽

History Of ◽

The Difference

Abstract Background: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease that affects approximately one in 500 people. HCM is a recognized genetic disorder most often caused by mutations involving myosin-binding protein C (MYBPC3) and β-myosin heavy chain (MYH7) which are responsible for approximately three-quarters of the identified mutations.Methods: As a part of the international multidisciplinary SILICOFCM project (www.silicofcm.eu) the present study evaluated the association between underlying genetic mutations and clinical phenotype in patients with HCM. Only patients with confirmed single pathogenic mutations in either MYBPC3 or MYH7 genes were included in the study and divided into two groups accordingly. The MYBPC3 group was comprised of 48 patients (76%), while the MYH7 group included 15 patients (24%). Each patient underwent clinical examination and echocardiography.Results: The most prevalent symptom in patients with MYBPC3 was dyspnea (44%), whereas in patients with MYH7 it was palpitations (33%). The MYBPC3 group had a significantly higher number of patients with a positive family history of HCM (46% vs. 7%; p=0.014). There was a numerically higher prevalence of atrial fibrillation in the MYH7 group (60% vs. 35%, p=0.085). Laboratory analyses revealed normal levels of creatinine (85.5±18.3 vs. 81.3±16.4 µmol/l; p=0.487) and blood urea nitrogen (10.2±15.6 vs. 6.9±3.9 mmol/l; p=0.472) which were similar in both groups. The systolic anterior motion presence was significantly more frequent in patients caring MYH7 mutation (33% vs. 10%; p=0.025), as well as mitral leaflet abnormalities (40% vs. 19%; p=0.039). Calcifications of mitral annulus were registered only in MYH7 patients (20% vs. 0%; p=0.001). The difference in diastolic function, i.e. E/e’ ratio between the two groups was also noted (MYBPC3 8.8±3.3, MYH7 13.9±6.9, p=0.079).Conclusions: Major findings of the present study corroborate the notion that MYH7 gene mutation patients are presented with more pronounced disease severity than those with MYBPC3.

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Genetic Determinants of Clinical Phenotype in Hypertrophic Cardiomyopathy

10.21203/rs.3.rs-36810/v5 ◽

2020 ◽

Author(s):

Lazar Velicki ◽

Djordje G Jakovljevic ◽

Andrej Preveden ◽

Miodrag Golubovic ◽

Marija Bjelobrk ◽

...

Keyword(s):

Hypertrophic Cardiomyopathy ◽

Clinical Phenotype ◽

Genetic Disorder ◽

Positive Family History ◽

Mitral Annulus ◽

Genetic Determinants ◽

Myosin Binding Protein ◽

Number Of Patients ◽

History Of ◽

The Difference

Abstract Background: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease that affects approximately one in 500 people. HCM is a recognized genetic disorder most often caused by mutations involving myosin-binding protein C (MYBPC3) and β-myosin heavy chain (MYH7) which are responsible for approximately three-quarters of the identified mutations.Methods: As a part of the international multidisciplinary SILICOFCM project (www.silicofcm.eu) the present study evaluated the association between underlying genetic mutations and clinical phenotype in patients with HCM. Only patients with confirmed single pathogenic mutations in either MYBPC3 or MYH7 genes were included in the study and divided into two groups accordingly. The MYBPC3 group was comprised of 48 patients (76%), while the MYH7 group included 15 patients (24%). Each patient underwent clinical examination and echocardiography.Results: The most prevalent symptom in patients with MYBPC3 was dyspnea (44%), whereas in patients with MYH7 it was palpitations (33%). The MYBPC3 group had a significantly higher number of patients with a positive family history of HCM (46% vs. 7%; p=0.014). There was a numerically higher prevalence of atrial fibrillation in the MYH7 group (60% vs. 35%, p=0.085). Laboratory analyses revealed normal levels of creatinine (85.5±18.3 vs. 81.3±16.4 µmol/l; p=0.487) and blood urea nitrogen (10.2±15.6 vs. 6.9±3.9 mmol/l; p=0.472) which were similar in both groups. The systolic anterior motion presence was significantly more frequent in patients carrying MYH7 mutation (33% vs. 10%; p=0.025), as well as mitral leaflet abnormalities (40% vs. 19%; p=0.039). Calcifications of mitral annulus were registered only in MYH7 patients (20% vs. 0%; p=0.001). The difference in diastolic function, i.e. E/e’ ratio between the two groups was also noted (MYBPC3 8.8±3.3, MYH7 13.9±6.9, p=0.079).Conclusions: Major findings of the present study corroborate the notion that MYH7 gene mutation patients are presented with more pronounced disease severity than those with MYBPC3.

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Raising awareness of the number of patients with multiple primary melanoma and a positive family history of melanoma

Journal of the American Academy of Dermatology ◽

10.1016/j.jaad.2015.02.381 ◽

2015 ◽

Vol 72 (5) ◽

pp. AB92

Keyword(s):

Family History ◽

Positive Family History ◽

Primary Melanoma ◽

Raising Awareness ◽

Number Of Patients ◽

Multiple Primary ◽

History Of

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An Unusual Presentation of a Myocardial Crypt in Hypertrophic Cardiomyopathy

Case Reports in Cardiology ◽

10.1155/2014/737052 ◽

2014 ◽

Vol 2014 ◽

pp. 1-3

Author(s):

Danny A. J. P. van de Sande ◽

Jan Hoogsteen ◽

Luc J. H. J. Theunissen

Keyword(s):

Hypertrophic Cardiomyopathy ◽

Interventricular Septum ◽

Positive Family History ◽

Phenotypic Expression ◽

Anterior Wall ◽

Left Ventricular ◽

Genes Encoding ◽

History Of ◽

Basal Septum ◽

Myocardial Crypts

Hypertrophic cardiomyopathy (HCM) is a common inherited cardiovascular disease with prevalence of 0.2% in the population. More than 1000 mutations in more than 10 genes encoding for proteins of the cardiac sarcomere have been identified. Cardiac magnetic resonance imaging (CMR) is used to characterize left ventricular morphology with great precision in patients with HCM and it identifies unique structural abnormalities in patients with HCM. We present a case of a 56-year-old man who had positive family history of HCM who was a carrier of the genetic MYH-7 2770 G > C, exon 23 mutation. Transthoracic echocardiography showed thickening of the interventricular septum (16 mm) and in particular the basal septum. CMR confirmed the diagnosis of HCM in the anteroseptal myocardium with a thickness of 23 mm and also revealed large and deep myocardial crypts in the anterior wall. These myocardial crypts are rarely found in the so-called genotype positive and phenotype positive patients, as in our case. Also the crypts in this case are deeper and wider than those reported in other cases. So in conclusion, this case reveals an uncommon finding of a myocardial crypt at an unusual myocardial site with the unusual morphology in a patient with genotypic and phenotypic expression of hypertrophic cardiomyopathy.

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Dermatoglyphics in Schizophrenia: The Relevance of Positive Family History

The British Journal of Psychiatry ◽

10.1192/bjp.130.1.56 ◽

1977 ◽

Vol 130 (1) ◽

pp. 56-58 ◽

Cited By ~ 5

Author(s):

R. Srinivasa Murthy ◽

N. N. Wig

Keyword(s):

Family History ◽

Positive Family History ◽

History Of ◽

The Difference

SummaryIn the present study dermatoglyphic features were studied in schizophrenics with and without positive family history of schizophrenia. It was found that the difference between normals and schizophrenics was further exaggerated in those schizophrenics with a positive family history for schizophrenia. The implications of the findings and the need for further work are highlighted.

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Evaluation of multiple risk factors involved in the development of Diabetic Retinopathy

Pakistan Journal of Medical Sciences ◽

10.12669/pjms.35.1.279 ◽

2019 ◽

Vol 35 (1) ◽

Cited By ~ 2

Author(s):

Syeda Birjees Anwar ◽

Naveed Asif ◽

Syed Abid Hassan Naqvi ◽

Sidra Malik

Keyword(s):

Risk Factors ◽

Diabetic Retinopathy ◽

Family History ◽

Positive Family History ◽

Family History Of Diabetes ◽

Duration Of Diabetes ◽

Multiple Risk Factors ◽

History Of ◽

The Mean ◽

The Difference

Objective: To determine the role of hypertension, hyperlipidemia, smoking and positive family history of diabetes and hypertension in the development of diabetic retinopathy. Methods: This prospective cohort study was conducted at the Department of Chemical Pathology, Armed Forces Institute of Pathology, Rawalpindi over 2 years period from June 2014 to June 2016. One hundred consecutive diabetic patients with no signs of diabetic retinopathy and good glycemic control (HbA1c<6.5%) were registered by non-probability convenient sampling after taking written informed consent. They were evaluated for hypertension, hyperlipidemia and smoking status. These patients were then followed 6 monthly for 2 years to look for the development of diabetic retinopathy. Results: The mean age of the patients was 50.72±9.29 years and there were 57 (57%) male and 43 (43%) female patients. Majority (82%) of the patients had NIDDM. The mean duration of diabetes was 8.31±6.83 years. 11% of the patients were smoker, 37% were hypertensive, 6% had hyperlipidaemia, 62% had family history of diabetes and 30% had family history of hypertension. At the end of follow-up, 9 (9.0%) patients had diabetic retinopathy. The frequency of diabetic retinopathy increased with increasing age of the patient; however, the difference was statistically insignificant. A comparatively higher frequency of diabetic retinopathy was also seen in patients with IDDM and those with positive family history of diabetes and hypertension yet again, the difference was statistically insignificant. Also, no significant difference was noted among male and female genders and smokers vs. non-smoker. However, the frequency of diabetic retinopathy increased significantly with increasing duration of diabetes. It was also higher among those with hypertension and hyperlipidemia. Conclusion: Higher patient age (≥50 years), increasing duration of diabetes (≥20 years), insulin dependent diabetes mellitus, hypertension, hyperlipidemia, and positive family history of diabetes and hypertension were found to be associated with increased frequency of diabetic retinopathy. How to cite this:Anwar SB, Asif N, Naqvi SAH, Malik S. Evaluation of multiple risk factors involved in the development of Diabetic Retinopathy. Pak J Med Sci. 2019;35(1):---------. doi: https://doi.org/10.12669/pjms.35.1.279 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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A Novel Mutation in Aicardi–Goutières' Syndrome: A Case Report

Journal of Pediatric Neurology ◽

10.1055/s-0040-1716910 ◽

2020 ◽

Author(s):

Motahareh Sheikh-Hosseini ◽

Mohammad Moarefzadeh ◽

Hamideh Alavi-Moghaddam ◽

Saeid Morovvati

Keyword(s):

Neonatal Jaundice ◽

Clinical Phenotype ◽

Novel Mutation ◽

Genetic Disorder ◽

Cerebral Atrophy ◽

Pathogenic Mutation ◽

Consanguineous Marriage ◽

The Other ◽

Congenital Infections ◽

History Of

AbstractAicardi–Goutières' syndrome (AGS) is a rare heterogeneous genetic disorder characterized by encephalopathy and may bear resemblance to congenital infections. The prevalence of AGS is estimated at more than 4,000 worldwide. Mutations in TREX1 gene are present in ∼22% of patients. We present the case of a 2-year-old boy who came to the Biogene laboratory (Tehran, Iran) with a constellation of congenital disorders but no clear diagnosis. His clinical phenotype consisted of neonatal jaundice, relative microcephaly with diffuse cerebral atrophy in both hemispheres, developmental delay, hypotonia, and nystagmus. There was history of parental consanguineous marriage and prematurity. In our study, a homozygous potentially pathogenic mutation in TREX1 gene associated with AGS1 was detected. This mutation has not been reported in the other patients with AGS. A novel frameshift homozygous potentially pathogenic mutation in TREX1 is postulated to be the cause of disease in our patient.

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