Publications by authors named "Ari Horton"

Purpose: The Australian Genomics Cardiovascular Disorders Flagship was a national multidisciplinary collaboration. It aimed to investigate the feasibility of genome sequencing (GS) and functional genomics to resolve variants of uncertain significance (VUS) in the clinical management of patients and families with cardiomyopathies, primary arrhythmias, and congenital heart disease (CHD).

Methods: Between April 2019 and December 2021, 600 probands meeting cardiovascular disorder criteria from 17 cardiology and genetics clinics across Australia were enrolled in the Flagship and underwent GS.

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  • Chromosome 22q11.2 deletion syndrome (22q11DS) is a common genetic condition often identified in infants, but many cases are diagnosed later in life, especially during adolescence and adulthood.
  • A study analyzed patients diagnosed after age 13 from 2010-2021 in Melbourne, revealing key clinical features like intellectual disability, hypocalcaemia, and facial dysmorphism in late-diagnosed individuals, while traditional signs like cardiac defects may be absent in adults.
  • The findings emphasize the condition's complex and varied symptoms, highlighting the need for awareness of atypical presentations to reduce underdiagnosis.
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Mitral regurgitation (MR) is the most common lesion in children with rheumatic heart disease (RHD). Progression of RHD results in the need for surgical intervention, the timing of which is dictated by left ventricular dilatation and the onset of heart failure symptoms. We sought to determine whether elevation in trans-mitral pressure gradient (TMPG) in those with moderate or severe rheumatic MR without significant mitral stenosis (MS) could predict the need for future surgical intervention.

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  • Pathogenic variants in the desmoplakin (DSP) gene lead to a unique type of cardiomyopathy that doesn't fit neatly into existing categories like DCM, NDLVC, or ARVC, with limited past studies on potential predictors of severe outcomes.
  • Researchers analyzed 800 patients with DSP variants from a global network over an average of 3.7 years, finding that 17.4% experienced sustained ventricular arrhythmias (VAs) and 9.0% had heart failure (HF) hospitalizations.
  • Key risk factors for developing VAs included female sex, history of non-sustained and sustained VAs, and lower left ventricular ejection fraction, while T-wave inversion was linked to HF
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  • Pathogenic variants in the desmoplakin (DSP) gene are linked to a specific type of arrhythmogenic cardiomyopathy, which increases the risk of serious heart rhythm issues, but current evaluation methods are unreliable for these patients.
  • A study was conducted with patients from the DSP-ERADOS registry to track the occurrence of sustained ventricular arrhythmia (VA) over time, using a detailed statistical analysis to create a new clinical prediction tool.
  • The research identified five key clinical factors that can help predict the risk of developing sustained VA, resulting in a new DSP risk score that demonstrated strong prediction capabilities in both the initial and external testing groups.
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  • * Recognizing these features helps both genetic and non-genetic specialists to detect cancers early, leading to better patient outcomes through timely interventions.
  • * Advances in genetic testing and risk-reducing treatments underscore the importance of knowing the facial and other physical signs of high-risk cancer syndromes for improved diagnosis and screening.
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Purpose: Gene selection for genomic newborn screening (gNBS) underpins the validity, acceptability, and ethical application of this technology. Existing gNBS gene lists are highly variable despite being based on shared principles of gene-disease validity, treatability, and age of onset. This study aimed to curate a gNBS gene list that builds upon existing efforts and provide a core consensus list of gene-disease pairs assessed by multiple expert groups worldwide.

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Background: Familial hypercholesterolaemia (FH) is a genetic condition that is a preventable cause of premature cardiovascular morbidity and mortality. High-level evidence and clinical practice guidelines support preventative care for people with FH. However, it is estimated that less than 10% of people at risk of FH have been detected using any approach across Australian health settings.

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Genetic risk information for medically actionable conditions has relevance for patients' blood relatives. However, cascade testing uptake in at-risk families is <50%, and the burden of contacting relatives is a significant barrier to dissemination of risk information. Health professionals (HPs) could notify at-risk relatives directly, with patients' consent.

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The clinical outcome for children and adolescents with homozygous familial hypercholesterolaemia (HoFH) can be devastating, and treatment options are limited in the presence of a null variant. In HoFH, atherosclerotic risk accumulates from birth. Gene therapy is an appealing treatment option as restoration of low-density lipoprotein receptor (LDLR) gene function could provide a cure for HoFH.

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Background: Early detection of rheumatic heart disease (RHD) through echocardiographic screening can facilitate early access to effective treatment, which reduces the risk for progression. Accurate, feasible approaches to echocardiographic screening that can be incorporated into routine health services are needed. The authors hypothesized that offsite expert review could improve the diagnostic accuracy of nonexpert-obtained echocardiographic images.

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  • The study aimed to analyze the occurrence and clinical characteristics of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) among children and teens in Victoria, Australia, from 2010 to 2019.
  • Researchers conducted a retrospective audit, reviewing cases from local hospitals and collecting data on demographics, clinical features, and management strategies.
  • Findings revealed a notable incidence of ARF, especially among Aboriginal, Torres Strait Islander, and Pacific Islander communities, along with significant disease severity in patients, highlighting the need for specialized services to manage and prevent these conditions.
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Transthoracic echocardiography is commonly used to identify structural and functional cardiac abnormalities that can be prevalent in childhood chronic kidney failure (KF). Left ventricular mass (LVM) increase is most frequently reported and may persist post-kidney transplant especially with hypertension and obesity. While systolic dysfunction is infrequently seen in childhood chronic KF, systolic strain identified by speckle tracking echocardiography has been frequently identified in dialysis and it can also persist post-transplant.

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  • * In Australia and New Zealand, an estimated 22,000 children and teens have FH, yet many go unnoticed until later in life or after heart problems arise.
  • * The paper aims to boost awareness and provide practical guidelines for diagnosing and managing FH in young people, including the use of treatments and genetic testing, while emphasizing the need for targeted detection and tailored care models to improve health outcomes.
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  • The text mentions a correction to a previously published article with the DOI: 10.1016/j.ajpc.2021.100151.
  • This correction suggests that there were errors or inaccuracies in the original article that needed to be addressed.
  • The updated information is important for researchers and readers who rely on the findings of that specific study.
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Background: The East Timor Hearts Fund has provided cardiac services in Timor-Leste since 2010, conducting three clinics yearly.

Aim: To develop collaborative telehealth services between Australia and Timor-Leste in the context of international border closures due to the COVID-19 pandemic.

Methods: Scoping discussions identified major challenges (structural, patient related and medical system related).

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Ethylmalonic encephalopathy (MIM #602473) is a rare autosomal recessive metabolic condition caused by biallelic variants in (MIM #608451), characterized by global developmental delay, infantile hypotonia, seizures, and microvascular damage. The microvascular changes result in a pattern of relapsing spontaneous diffuse petechiae and purpura, positional acrocyanosis, and pedal edema, hemorrhagic suffusions of mucous membranes, and chronic diarrhea. Here, we describe an instructive case in which ethylmalonic encephalopathy masqueraded as meningococcal septicemia and shock.

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Purpose: Genetic variants causing aberrant premessenger RNA splicing are increasingly being recognized as causal variants in genetic disorders. In this study, we devise standardized practices for polymerase chain reaction (PCR)-based RNA diagnostics using clinically accessible specimens (blood, fibroblasts, urothelia, biopsy).

Methods: A total of 74 families with diverse monogenic conditions (31% prenatal-congenital onset, 47% early childhood, and 22% teenage-adult onset) were triaged into PCR-based RNA testing, with comparative RNA sequencing for 19 cases.

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Background: Echocardiographic screening can detect asymptomatic cases of rheumatic heart disease (RHD), facilitating access to treatment. Barriers to implementation of echocardiographic screening include the requirement for expensive equipment and expert practitioners. We aimed to evaluate the diagnostic accuracy of an abbreviated echocardiographic screening protocol (single parasternal-long-axis view with a sweep of the heart) performed by briefly trained, nonexpert practitioners using handheld ultrasound devices.

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