Publications (4)31.29 Total impact
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Article: Mutations in sarcomere protein genes in left ventricular noncompaction.
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ABSTRACT: Left ventricular noncompaction constitutes a primary cardiomyopathy characterized by a severely thickened, 2-layered myocardium, numerous prominent trabeculations, and deep intertrabecular recesses. The genetic basis of this cardiomyopathy is still largely unresolved. We speculated that mutations in sarcomere protein genes known to cause hypertrophic cardiomyopathy and dilated cardiomyopathy may be associated with left ventricular noncompaction. Mutational analysis in a cohort of 63 unrelated adult probands with left ventricular noncompaction and no other congenital heart anomalies was performed by denaturing high-performance liquid chromatography analysis and direct DNA sequencing of 6 genes encoding sarcomere proteins. Heterozygous mutations were identified in 11 of 63 samples in genes encoding beta-myosin heavy chain (MYH7), alpha-cardiac actin (ACTC), and cardiac troponin T (TNNT2). Nine distinct mutations, 7 of them in MYH7, 1 in ACTC, and 1 in TNNT2, were found. Clinical evaluations demonstrated familial disease in 6 of 11 probands with sarcomere gene mutations. MYH7 mutations segregated with the disease in 4 autosomal dominant LVNC kindreds. Six of the MYH7 mutations were novel, and 1 encodes a splice-site mutation, a relatively unique finding for MYH7 mutations. Modified residues in beta-myosin heavy chain were located mainly within the ATP binding site. We conclude that left ventricular noncompaction is within the diverse spectrum of cardiac morphologies triggered by sarcomere protein gene defects. Our findings support the hypothesis that there is a shared molecular etiology of different cardiomyopathic phenotypes.Circulation 07/2008; 117(22):2893-901. · 14.74 Impact Factor -
Article: Pulmonary hypertension in a case of Hb-Mainz hemolytic anemia.
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ABSTRACT: The development of pulmonary arterial hypertension (PAH) is the leading cause of mortality in patients with thalassemia and sickle cell anemia and was reported to occur in hemolytic anemias such as hereditary stomatocytosis, and paroxysmal nocturnal hemoglobinuria. Here, we report for the first time on the development of PAH in a patient with Hb-Mainz hemolytic anemia. Hb-Mainz is an unstable hemoglobin variant resulting from mutations at codon 98 of the beta chain gene (Val>Glu) characterized by severe chronic hemolytic anemia. The development of PAH in this patient further supports the contention that there is a clinical syndrome of hemolysis-associated development of PAH.Journal of Pediatric Hematology/Oncology 03/2007; 29(3):173-7. · 1.16 Impact Factor -
Article: A novel locus for dilated cardiomyopathy, diffuse myocardial fibrosis, and sudden death on chromosome 10q25-26.
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ABSTRACT: We sought to identify the genetic locus for an inherited form of dilated cardiomyopathy (DCM) that is characterized by diffuse myocardial fibrosis and sudden death. Genetic studies have mapped multiple loci for DCM, which is a major cause of nonischemic heart failure; however, the genes responsible for the majority of cases have yet to be identified. Sixty-six family members were evaluated by 12-lead electrocardiogram (ECG), echocardiogram, and laboratory studies. Individuals with echocardiographically documented DCM were defined as affected. Subjects were considered unaffected if they were older than 20 years of age, had a normal ECG and echocardiogram, no personal history of heart failure, and had no affected offspring. Genotyping was performed using polymorphic markers. Genome-wide linkage analysis identified a novel locus for this inherited phenotype on chromosome 10q25.3-q26.13. Peak two-point logarithm of the odds scores >3.0 were obtained independently with each family using the markers D10S1773 and D10S1483, respectively. Haplotype analyses defined a critical interval of 14.0 centiMorgans between D10S1237 and D10S1723, corresponding to a physical distance of 9.5 megabases. Multipoint linkage analyses confirmed this interval and generated a peak logarithm of the odds score of 8.2 indicating odds of >100,000,000:1 in favor of this interval as the location of the gene defect responsible for DCM in these families. We have mapped a novel locus for cardiomyopathy, diffuse myocardial fibrosis, and sudden death to chromosome 10q25-q26. The identification of the causative gene in this interval will be an important step in understanding the fundamental mechanisms of heart failure and sudden death.Journal of the American College of Cardiology 08/2006; 48(1):106-11. · 14.16 Impact Factor -
Article: Diagnostic Catheterization and Balloon Sizing of Atrial Septal Defects by Echocardiography Guidance Without Fluoroscopy
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ABSTRACT: To avoid x-ray exposure prior to interventional closure of atrial septal defects (ASDs), we recently developed a technique for diagnostic catheterization and balloon sizing of the defect by echocardiography guidance without fluoroscopy. We report on our first experiences with this technique. Fourteen patients with atrial septal perforations (mean age, 23 years; range, 1–66 years) underwent diagnostic catheterization and balloon sizing prior to possible interventional defect closure. Mean size of the defects was 16 mm (7–29 mm). Mean left-to-right shunt was Qp/Qs =2.0 (range, 1.0–4.0). Without fluoroscopy, the procedures were performed in two children by transthoracic echocardiography (TTE) and in 12 patients by both TTE and transesophageal echocardiography (TEE). Mean procedure time was 59 minutes (range, 35–90 minutes). We conclude that oxymetry, pressure recordings, and the estimation of the balloon-stretched size of atrial septal perforations can be performed safely by echocardiographic guidance without fluoroscopy. The x-ray exposure for patient selection prior to a transcatheter closure of an ASD can be avoided with this technique.Echocardiography 01/2000; 17(2):159 - 163. · 1.24 Impact Factor
