Human genetics
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Stillbirth after 20 weeks gestation happens in 1 in 200 pregnancies and occurs more commonly than neonatal loss and sudden infant death syndrome (SIDs) combined. The stillbirth rate is several times greater in low as opposed to high-resource countries. However, among high-resource countries, although a lower overall stillbirth rate exists, there has been little change for several decades. ⋯ The channelopathy disorders are included as initial examples of genetic conditions with variable presentation including an association with sudden infant death syndrome. Highlighted are the challenges when numerous genes and variants are involved, and the task of assigning pathogenicity. The advantages and limitations of genetic evaluations are presented and avenues for further research considered.
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In the field of cancer genomics, the broad availability of genetic information offered by next-generation sequencing technologies and rapid growth in biomedical publication has led to the advent of the big-data era. Integration of artificial intelligence (AI) approaches such as machine learning, deep learning, and natural language processing (NLP) to tackle the challenges of scalability and high dimensionality of data and to transform big data into clinically actionable knowledge is expanding and becoming the foundation of precision medicine. In this paper, we review the current status and future directions of AI application in cancer genomics within the context of workflows to integrate genomic analysis for precision cancer care. ⋯ Publicly available tools or algorithms for key NLP technologies in the literature mining for evidence-based clinical recommendations are reviewed and compared. In addition, the present paper highlights the challenges to AI adoption in digital healthcare with regard to data requirements, algorithmic transparency, reproducibility, and real-world assessment, and discusses the importance of preparing patients and physicians for modern digitized healthcare. We believe that AI will remain the main driver to healthcare transformation toward precision medicine, yet the unprecedented challenges posed should be addressed to ensure safety and beneficial impact to healthcare.
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Canada's regulatory frameworks governing privacy and research are generally permissive of genomic data sharing, though they may soon be tightened in response to public concerns over commercial data handling practices and the strengthening of influential European privacy laws. Regulation can seem complex and uncertain, in part because of the constitutional division of power between federal and provincial governments over both privacy and health care. Broad consent is commonly practiced in genomic research, but without explicit regulatory recognition, it is often scrutinized by research or privacy oversight bodies. ⋯ For the moment, Canada's commercial sector is recognized as "adequate" by Europe, facilitating import of European data. Maintaining adequacy status under the new European General Data Protection Regulation (GDPR) is a concern because of Canada's weaker individual rights, privacy protections, and regulatory enforcement. Researchers must stay attuned to shifting international and national regulations to ensure a sustainable future for responsible genomic data sharing.
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Christianson syndrome (OMIM 300243), caused by mutations in the X-linked SLC9A6 gene, is characterized by severe global developmental delay and intellectual disability, developmental regression, epilepsy, microcephaly and impaired ocular movements. It shares many common features with Angelman syndrome. Carrier females have been described as having learning difficulties with mild to moderate intellectual disability, behavioural issues and psychiatric illnesses. ⋯ E64X mutation known to cause a premature stop codon in SLC9A6. We characterize and expand the clinical phenotype of female SLC9A6 mutation carriers by comparing our described family with female carriers previously discussed in the literature. In particular, we highlight the neurodevelopmental and psychiatric phenotypes observed in our family and previous reports.
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Pulmonary arterial hypertension (PAH) is a rare disease characterized by distinctive changes in pulmonary arterioles that lead to progressive elevation of pulmonary artery pressure, pulmonary vascular resistance, right ventricular failure, and a high mortality rate. The etiology of PAH is heterogeneous and incompletely understood. Based on clinical classification, WHO Group 1 PAH includes sporadic disease (idiopathic PAH), inherited PAH (heritable PAH), and association with certain medical conditions (associated PAH). ⋯ In addition to rare mutations as a monogenic cause of HPAH, common variants in cerebellin 2 (CBLN2) increase the risk of PAH by approximately twofold. PAH in children is much more heterogeneous than in adults and can be associated with several genetic syndromes, specifically syndromes with congenital heart disease, vascular disease, and hepatic disease. Clinical genetic testing is available for PAH and should be considered in families to allow for more definitive risk stratification and allow for reproductive planning.