Purpose The purpose of this study is to use a genotype-first approach to explore highly penetrant, autosomal dominant cardiovascular diseases with external features, the RASopathies and Marfan syndrome (MFS), using biobank data. Methods This study uses exome sequencing and corresponding phenotypic data from Mount Sinai's BioMe(n = 32,344) and the U...
Published in Cardiovascular research
The genetic cause of cardiac conduction system disease (CCSD) has not been fully elucidated. Whole-exome sequencing (WES) can detect various genetic variants; however, the identification of pathogenic variants remains a challenge. We aimed to identify pathogenic or likely pathogenic variants in CCSD patients by using WES and 2015 American College o...
Published in Orphanet Journal of Rare Diseases
BackgroundAortic root dilatation and—dissection and mitral valve prolapse are established cardiovascular manifestations in Marfan syndrome (MFS). Heart failure and arrhythmic sudden cardiac death have emerged as additional causes of morbidity and mortality.MethodsTo characterize myocardial dysfunction and arrhythmia in MFS we conducted a prospectiv...
OBJECTIVES: The clinical heterogeneity of frontotemporal dementia (FTD) complicates identification of biomarkers for clinical trials that may be sensitive during the prediagnostic stage. It is not known whether cognitive or behavioural changes during the preclinical period are predictive of genetic status or conversion to clinical FTD. The first ob...
Background: Accurate discrimination of benign and pathogenic rare variation remains a priority for clinical genome interpretation. State-of-the-art machine learning tools are useful for genome-wide variant prioritisation but remain imprecise. Since the relationship between molecular consequence and likelihood of pathogenicity varies between genes w...
Domestic animal populations are often characterised by high rates of inbreeding and low effective population sizes due to selective breeding practices. These practices can result in otherwise rare recessive deleterious alleles drifting to high frequencies, resulting in reduced fertility rates. This study aimed to identify potential recessive lethal...
Epigenetic regulation involves changes in gene expression independent of DNA sequence variation that are inherited through cell division. In addition to a fundamental role in cell differentiation, some epigenetic changes can also be transmitted transgenerationally through meiosis. Epigenetic alterations (epimutations) could thus contribute to herit...
The human- and animal-adapted lineages of the Mycobacterium tuberculosis complex (MTBC) are thought to have expanded from a common progenitor in Africa. However, the molecular events that accompanied this emergence remain largely unknown. Here, we describe two MTBC strains isolated from patients with multidrug resistant tuberculosis, representing a...
Oncogenic transformation is associated with profound changes in cellular metabolism, but whether tracking these can improve disease stratification or influence therapy decision-making is largely unknown. Using the iKnife to sample the aerosol of cauterized specimens, we demonstrate a new mode of real-time diagnosis, coupling metabolic phenotype to ...
OBJECTIVE: C9orf72 expansion is the most common genetic cause of frontotemporal dementia (FTD). We examined aging trajectories of cortical thickness (CTh) and surface area in C9orf72 expansion adult carriers compared to healthy controls to characterize preclinical cerebral changes leading to symptoms. METHODS: Data were obtained from the Genetic Fr...
