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Background: With expanding use of clinical whole exome sequencing (WES), genetic variants of uncertain significance are increasingly identified. As pathologic mutations in genes associated with arrhythmogenic right ventricular cardiomyopathy (ARVC) carry a risk of sudden death, determining the diagnostic relevance of incidentally identified variants associated with these genes is critical. Methods: WES variants from a large, predominantly pediatric cohort (N = 7,066 probands) were obtained for nine ARVC‐associated genes (Baylor Miraca). For comparison, a control cohort was derived from the gnomAD database and an ARVC case cohort (N = 1,379 probands) was established from ARVC cases in the literature. Topologic mapping was performed and signal‐to‐noise analysis was conducted normalizing WES, or case variants, against control variant frequencies. Retrospective chart review was performed of WES cases evaluated clinically (Texas Children's Hospital). Results: Incidentally identified variants occurred in 14% of WES referrals and localized to genes which were rare among ARVC cases yet similar to controls. Amino acid‐level signal‐to‐noise analysis of cases demonstrated "pathologic hotspots" localizing to critical domains of PKP2 and DSG2 while WES variants did not. PKP2 ARM7 and ARM8 domains and DSG2 N‐terminal cadherin‐repeat domains demonstrated high pathogenicity while normalized WES variant frequency was low. Review of clinical data available on WES referrals demonstrated none with evidence of ARVC among variant‐positive individuals. Conclusions: Incidentally identified variants are common among pediatric WES testing with gene frequencies similar to "background" variants. Incidentally identified variants are unlikely to be pathologic. [ABSTRACT FROM AUTHOR]

Malnutrition contributes to nearly half of all preventable deaths in children under the age of five. While the burden of disease is heaviest in Sub-Saharan Africa, South, and Southeast Asia, malnutrition in Latin America remains high, especially within indigenous communities. This study evaluates the prevalence of malnutrition and its relationship with access to healthcare resources within 172 indigenous Wayuú communities in La Guajira, Colombia. Healthcare workers administered a health questionnaire and collected anthropometric measurements on all children 6 months to 5 years of age within the Wayuú households. These data were utilised to calculate the prevalence of acute malnutrition, stunting, and underweight. Of all surveyed Wayuú children, 22.9% and 18.3% met criteria for moderate and severe malnutrition, 33.4% and 28.1% met criteria for moderate and severe stunting, and 28.1% and 16.6% were moderately and severely underweight. Across all categories, malnourished children were older, less likely to have had a medical professional present at birth, less likely to have received medical care after birth, and more likely to have been born in a non-medical, community setting. The prevalence of malnutrition is much higher than national levels in Colombia. This population requires urgent assistance to address their disproportionately high rates of malnutrition. [ABSTRACT FROM AUTHOR]