Robert B Hinton

..We describe a patient with a pathogenic familial beta-myosin heavy chain mutation who was prenatally diagnosed with left ventricular hypoplasia and restrictive diastolic physiology...

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

..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...

..The increasing use of genetic screening promises to cultivate a paradigm shift in medical treatment emphasizing primary prevention and early intervention. Appreciation of the family history is necessary to make this important advance...

....

..Combining molecular and engineering approaches provides complementary mechanistic insights that may be informative in the search for new therapeutic targets and durable valve bioprostheses...

..These findings provide specific molecular indicators of AoVD progression, which may lead to identification of early disease markers and the development of potential therapeutics...

..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)...

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

..Overall, these data implicate Twist1 as a critical regulator of valve development and suggest that Twist1 influences ECM production and cell proliferation during disease...

..A research-based pediatric cardiomyopathy registry identified familial, syndromic, or metabolic causes in 30% of children. However, these results predated clinical genetic testing...

..The micropipette aspiration technique provides a promising approach for studies of valve structure and function in small animal models, such as transgenic mouse models of 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...

..Further studies are necessary to determine regulatory pathway interactions underlying valve pathogenesis in order to generate new avenues for novel therapeutics...

....

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

..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...

..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...

..Finally, we believe cardiac defects with this genetic syndrome are a poor prognostic finding associated with high mortality...

..Because of potential new therapies, it is increasingly important to recognize neonatal MFS in utero as well as shortly after birth to initiate the appropriate diagnostic work-up and management...

....

..Progesterone differentially regulates the expression of PGE2 receptor isoforms in the cervix. Elucidating the regulation of PGE2 receptors may facilitate improved approaches to the prevention and treatment of preterm labor...

..Collectively, our studies have identified an in vivo requirement for scx during valvulogenesis and demonstrate its role in cell lineage differentiation and matrix distribution in remodeling valve structures...

..A Career Development Award will allow the Candidate to devote 80% effort to patient-oriented research, and to obtain the training necessary to transition to an independent investigator. (End of Abstract) ..