D Woodrow Benson

..We hypothesized that mechanical dyssynchrony is present in DMD patients and that cardiovascular magnetic resonance (CMR) may predict CRT efficacy...

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..Our findings reveal a molecular basis for some forms of congenital SSS and define a recessive disorder of a human heart voltage-gated sodium channel...

..5, illustrate these accomplishments and at the same time provide a forecast of the nature of future genetic studies to better understand the origins of pediatric heart disease...

..T2 maps of the LV were generated for all subjects using a black blood dual spin echo method at two echo times. The full width at half maximum (FWHM) was calculated from a histogram of LV T2 distribution constructed for each subject...

..Serial epsilon(cc) measurements might provide reliable monitoring of the progression of DMD-associated cardiac dysfunction before overt heart failure develops, because it is more sensitive than the EF...

..These regions likely contain genes whose mutation results in BAV and/or associated CVM indicating their important role in valvulogenesis and cardiac development...

..This study was designed to identify disease loci for hypoplastic left heart syndrome (HLHS) and evaluate the genetic relationship between HLHS and bicuspid aortic valve (BAV)...

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..The candidate locus approach allowed an efficient mechanism to uncover the potassium channel mutation causing LQTS in this family...

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..This study sought to determine the size of the genetic effect (heritability) in families identified by a hypoplastic left heart syndrome (HLHS) proband...

..Brains from HLHS fetuses demonstrated chronic diffuse white matter injury of varying severity. These patterns of prenatal head growth and brain histopathology identify a spectrum of abnormal CNS development and/or injury in HLHS fetuses...

..These findings are significant as they provide insight into the molecular basis of a clinical condition previously defined only by biophysical characteristics...

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..The child was treated aggressively and is doing well at age 6 years...

..Arrhythmia documented during cardiac arrest is rapid ventricular tachycardia; ICD is effective therapy for cardiac arrest in patients with PVT due to KCNJ2 mutation...

..Because elastic fiber abnormalities are a central feature of degenerative valve disease, we hypothesized that elastin-insufficient mice would manifest viable heart valve disease...

..Histochemical analysis of the aortic valve revealed decreased and disorganized elastin with loss of the normal trilaminar cusp organization. These findings suggest that elastin has a role in the pathogenesis of semilunar valve disease...

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..The objective of this study was the clinical and genetic characterization of the family of an individual initially diagnosed as a child in 1978...

..This may be due to phenotypic and genetic heterogeneity of BAV and VSD, other modifying factors as manifested by differences in associated CVM, as well as limitations of the clinical taxonomy of VSD...

..Continuous inotrope infusion should be considered a practical treatment strategy for end stage cardiac dysfunction in Duchenne muscular dystrophy patients when cardiac transplantation is not a viable option...

..The heritability of BAV plus other cardiovascular anomalies suggests that valve malformation can be primary to defective valvulogenesis or secondary to other elements of cardiogenesis...

..ECG abnormalities are common in very young DMD patients, signaling cardiac involvement well before the onset of clinical symptoms...

..This study sought to evaluate the natural history of occult cardiac dysfunction in Duchenne muscular dystrophy (DMD)...

..1 current. These findings support the suggestion that, in addition to its recognized role in function of cardiac and skeletal muscle, KCNJ2 plays an important role in developmental signaling...

..Taken as a whole, the prospect of understanding the genetic basis of congenital heart disease and translating it into improved diagnostic and therapeutic strategies has never been better...

..The homozygous mutation results in absence of functional IKr, causing a profound loss of HERG channel function, creating the equivalent of a "HERG knockout" and leading to a severe phenotype...

..The data highlight the need for primary care physicians and specialists to familiarize themselves with the extracardiac stigmata of del22q11 to ensure timely diagnosis in all family members...

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..Here we review genetic, developmental, and biochemical studies of six cardiac transcription factors that have been identified as genetic causes for CHD in humans...

..BAV is determined largely by genetic effects, but the phenotypic variability of AVD is primarily determined by nongenetic factors. BAV morphology may have predictive value for the time course of AVD...

..Risk-stratification schemes for SCN5A mutation carriers remain uncertain...

..Issues surrounding the genetics of HLHS, developmental outcomes, and quality of life are addressed in addition to the many other considerations for caring for this group of complex patients...

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..Infants and children with repaired congenital diaphragmatic hernia (CDH) often continue to show delayed growth and development that may be, in part, secondary to unrecognized persistence of increased pulmonary vascular resistance (PVR)...

..Our results demonstrate severe cardiac dysfunction in Scgd(-/-) mice at 8 months. The study identifies a set of non-invasive markers that could be used to study efficacy of novel therapeutic agents in dystrophic mice...

..The purpose of this study was to estimate the frequency of NKX2.5 mutations in specific cardiovascular anomalies and investigate genotype-phenotype correlations in individuals with NKX2.5 mutations...

..5 mutant proteins would result in the ability to classify mutations according to function in a scheme that would help to clarify genotype-phenotype correlations. We analyzed missense mutations in the conserved homeodomain...

..These data provide insight into the distinct clinical phenotypes resulting from mutation of a single ion channel...

..Accordingly, loss of ventricular muscle cell lineage specification into trabecular and conduction system myocytes is a new mechanistic pathway for progressive cardiomyopathy and conduction defects in congenital heart disease...

..We conclude that a prerequisite for normal Purkinje fiber maturation is precise regulation of Nkx2-5 levels...

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..Genes causing long QT syndrome were used as candidate genes in 4 patients with bidirectional ventricular tachycardia. In 2 patients, we identified a common low penetrance HERG allele (R1047L) with an intermediate biophysical phenotype...

..The mutation and the polymorphism were both found in the same allele of a child with isolated conduction disease, suggesting a direct functional association between a polymorphism and a mutation in the same gene...

..The purpose of this research was to determine whether an intronic variant (T1945+6C) in KCNH2 is a disease-causing mutation, and if expanded phenotyping criteria produce improved identification of long QT syndrome (LQTS) patients...

..The normal QTc, distinct ECG, and other clinical features distinguish ATS1 from long-QT syndrome, and it is best designated as ATS1 rather than LQT7...

..C101R) exhibited impaired trafficking. Our results demonstrate functional consequences of two novel trafficking-competent KCNJ2 mutations associated with Andersen syndrome and expand our knowledge of allelic diversity in this disease...

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..Additional studies will be required to determine the degree to which GATA4 mutation contributes to human CHD characterized by ECD or RV hypoplasia...

..Receipt of the Mid-Career Award in patient-oriented research will allow the Candidate to devote 50% effort to research and mentoring in patient-oriented research. ..

..Completion of the proposed studies should greatly improve our understanding of ischemia-reperfusion injury and therapies to prevent LCOS following surgery with cardiopulmonary bypass in infants. (End of Abstract) ..