Atypical nested 22q11.2 duplications between LCR22B and LCR22D are associated with neurodevelopmental phenotypes including autism spectrum disorder with incomplete penetrance.

Background: Chromosome 22q11.2 is susceptible to genomic rearrangements and the most frequently reported involve deletions and duplications between low copy repeats LCR22A to LCR22D. Atypical nested deletions and duplications are rarer and can provide a valuable opportunity to investigate the dosage effects of a smaller subset of genes within the 22q11.

A review of structural brain abnormalities in Pallister-Killian syndrome.

Background: Pallister-Killian syndrome (PKS) is a rare multisystem developmental syndrome usually caused by mosaic tetrasomy of chromosome 12p that is known to be associated with neurological defects.

Methods: We describe two patients with PKS, one of whom has bilateral perisylvian polymicrogyria (PMG), the other with macrocephaly, enlarged lateral ventricles and hypogenesis of the corpus callosum. We have also summarized the current literature describing brain abnormalities in PKS.

Genotype and phenotype spectrum of NRAS germline variants.

RASopathies comprise a group of disorders clinically characterized by short stature, heart defects, facial dysmorphism, and varying degrees of intellectual disability and cancer predisposition. They are caused by germline variants in genes encoding key components or modulators of the highly conserved RAS-MAPK signalling pathway that lead to dysregulation of cell signal transmission. Germline changes in the genes encoding members of the RAS subfamily of GTPases are rare and associated with variable phenotypes of the RASopathy spectrum, ranging from Costello syndrome (HRAS variants) to Noonan and Cardiofaciocutaneous syndromes (KRAS variants).

Physical Activity and Survival among Long-term Cancer Survivor and Non-Cancer Cohorts.

Evidence suggests physical activity improves prognosis following cancer diagnosis; however, evidence regarding prognosis in long-term survivors of cancer is scarce. We assessed physical activity in 1,589 cancer survivors at an average 8.8 years following their initial diagnosis and calculated their future mortality risk following physical activity assessment.

The risk of re-identification versus the need to identify individuals in rare disease research.

There is a growing concern in the ethics literature and among policy makers that de-identification or coding of personal data and biospecimens is not sufficient for protecting research subjects from privacy invasions and possible breaches of confidentiality due to the possibility of unauthorized re-identification. At the same time, there is a need in medical science to be able to identify individual patients. In particular for rare disease research there is a special and well-documented need for research collaboration so that data and biosamples from multiple independent studies can be shared across borders.

Medium-term outcomes after pulmonary valve replacement with the Freestyle valve for congenital heart disease: a case series.

Objectives: The Freestyle valve may be used for pulmonary valve replacement (PVR). Whether its stentless design and anticalcification treatment improve durability relative to alternative bioprostheses, however, is unknown and long-term data are lacking.

Methods: We performed a retrospective review of all Freestyle PVRs performed by a single surgeon in two institutions.

The Human Phenotype Ontology: Semantic Unification of Common and Rare Disease.

The Human Phenotype Ontology (HPO) is widely used in the rare disease community for differential diagnostics, phenotype-driven analysis of next-generation sequence-variation data, and translational research, but a comparable resource has not been available for common disease. Here, we have developed a concept-recognition procedure that analyzes the frequencies of HPO disease annotations as identified in over five million PubMed abstracts by employing an iterative procedure to optimize precision and recall of the identified terms. We derived disease models for 3,145 common human diseases comprising a total of 132,006 HPO annotations.

The journey from traffic offender to severe road trauma victim: destiny or preventive opportunity?

Background: Road trauma is a leading cause of death and injury in young people. Traffic offences are common, but their importance as a risk indicator for subsequent road trauma is unknown. This cohort study assessed whether severe road trauma could be predicted by a history of prior traffic offences.

A germline MTOR mutation in Aboriginal Australian siblings with intellectual disability, dysmorphism, macrocephaly, and small thoraces.

We report on three Aboriginal Australian siblings with a unique phenotype which overlaps with known megalencephaly syndromes and RASopathies, including Costello syndrome. A gain-of-function mutation in MTOR was identified and represents the first reported human condition due to a germline, familial MTOR mutation. We describe the findings in this family to highlight that (i) the path to determination of pathogenicity was confounded by the lack of genomic reference data for Australian Aboriginals and that (ii) the disease biology, functional analyses in this family, and studies on the tuberous sclerosis complex support consideration of an mTOR inhibitor as a therapeutic agent.

Automatic concept recognition using the human phenotype ontology reference and test suite corpora.

Concept recognition tools rely on the availability of textual corpora to assess their performance and enable the identification of areas for improvement. Typically, corpora are developed for specific purposes, such as gene name recognition. Gene and protein name identification are longstanding goals of biomedical text mining, and therefore a number of different corpora exist.

Strategic information for hospital service planning: a linked data study to inform an urban Aboriginal Health Liaison Officer program in Western Australia.

Objectives: The aim of the present study was to provide descriptive planning data for a hospital-based Aboriginal Health Liaison Officer (AHLO) program, specifically quantifying episodes of care and outcomes within 28 days after discharge.

Methods: A follow-up study of Aboriginal in-patient hospital episodes was undertaken using person-based linked administrative data from four South Metropolitan hospitals in Perth, Western Australia (2006-11). Outcomes included 28-day deaths, emergency department (ED) presentations and in-patient re-admissions.

Role of international registries in enhancing the care of familial hypercholesterolaemia.

Familial hypercholesterolaemia (FH) is a relatively common genetic disorder associated with high risk of coronary heart disease that is preventable by early diagnosis and treatment. In a previous article, we reviewed the evidence for clinical management, models of care and health economic evaluations. The present commentary emphasises that collective action is needed to strengthen our approaches to evidence-based care, including better diagnosis and access to effective therapies.