The shape of things to come

see pages Towards a more representative morphology: clinical and ethical considerations for including diverse populations in diagnostic genetic atlases and An electronic atlas of human malformation syndromes in diverse populations

If humans come in a myriad of shapes and sizes, why do clinical diagnostic guidelines often not reflect that diversity? That simple question led a group of medical geneticists experienced in working in multicultural settings to compile such a resource, now available freely online (http://research.nhgri.nih.gov/atlas) and described here. The Atlas of Human Malformation Syndromes in Diverse Populations catalogs genetic syndromes and includes photographs of affected patients of various ethnicities. Registered users can search by phenotype, syndrome, ethnicity, and genetic diagnosis. The goal, according to the organizers at the National Human Genome Research Institute, is to provide a tool to clinicians in underresourced countries with few local medical geneticists available for consultations. The photos in this online resource have not previously been published and were obtained directly from clinicians throughout the world. The authors point out that although genomic medicine is rapidly expanding globally, its impact has not been felt in the underresourced countries where 80% of people live and 90% of births occur. In an accompanying review, Koretzky et al. ponder the ethical questions surrounding selection and portrayal of individuals in the atlas. They review the complex and sometimes troubled history of medicine and race politics and evaluate the ethical risks attendant with making identifiable pictures of individuals, many of whom are children with intellectual disabilities, available online. —Karyn Hede, News Editor

New clinically significant genetic variants found in Ehlers–Danlos syndrome

see page Targeted next-generation sequencing makes new molecular diagnoses and expands genotype–phenotype relationship in Ehlers–Danlos syndrome

A next-generation-sequencing (NGS) approach has revealed new, clinically actionable genetic variants in patients diagnosed with Ehlers–Danlos syndrome (EDS), the highly heterogeneous group of overlapping disorders of connective tissue. The new NGS panel, developed by a team including the National EDS Diagnostic Service in London, and reported in this issue, identified seven new pathogenic or likely-pathogenic variants that required clinical follow-up. Because EDS is associated with a high risk of life-threatening complications, including arterial aneurysm or rupture and bowel perforation, accurate diagnosis is paramount. The investigators developed an NGS panel that covers not only genes linked to EDS but also related genes with overlapping clinical manifestations. They recruited 177 unrelated patients referred to the National EDS Diagnostic Service with suspected EDS. Investigators were blinded to previous genetic testing results. The NGS panel identified all 22 pathogenic variants in collagen genes that had previously been sequenced using classical methods. Importantly, it also identified four additional potentially pathogenic variants in collagen genes not previously selected for sequencing and four additional variants in genes associated with risk of aortic rupture. The test also revealed 22 variants of uncertain significance. The results may help guide development of new genetic testing for EDS diagnosis. —Karyn Hede, News Editor