Inner Ear Malformations in Congenital Deafness Are Not Associated with Increased Risk of Breech Presentation

Background: There is speculation that an immature vestibular system may be associated with breech presentation at delivery. Our aim was to determine whether syndromes with congenital inner ear malformations were accompanied by a higher frequency of breech presentation/malpresentations than in the general population (2%−3%). Methods: A review was conducted for published literature using PubMed/MEDLINE (1936–2016), to determine frequency of breech presentation and transverse lie in cases with congenital deafness (Michel aplasia, Wildervanck syndrome, Mondini-Alexander dysplasia, Waardenburg syndrome, CHARGE syndrome, Large vestibular aqueductal syndrome, Pendred syndrome, Oculo-aurico-vertebral spectrum, Jervel and Lange-Nielsen syndrome, Usher syndrome, and Scheibe dysplasia) and vestibular nerve aplasia. Results: Identified were total of 122 cases. The frequency of breech presentation was 1.64%, and of transverse lie 1.64%, giving a total of 3.28% malpresentations. Conclusion: The results of the study suggest that congenital malformations of the vestibular apparatus are not associated with the increased risk of breech presentation at delivery

Plasma urate concentration and risk of coronary heart disease: a Mendelian randomisation analysis.

BACKGROUND: Increased circulating plasma urate concentration is associated with an increased risk of coronary heart disease, but the extent of any causative effect of urate on risk of coronary heart disease is still unclear. In this study, we aimed to clarify any causal role of urate on coronary heart disease risk using Mendelian randomisation analysis. METHODS: We first did a fixed-effects meta-analysis of the observational association of plasma urate and risk of coronary heart disease. We then used a conventional Mendelian randomisation approach to investigate the causal relevance using a genetic instrument based on 31 urate-associated single nucleotide polymorphisms (SNPs). To account for potential pleiotropic associations of certain SNPs with risk factors other than urate, we additionally did both a multivariable Mendelian randomisation analysis, in which the genetic associations of SNPs with systolic and diastolic blood pressure, HDL cholesterol, and triglycerides were included as covariates, and an Egger Mendelian randomisation (MR-Egger) analysis to estimate a causal effect accounting for unmeasured pleiotropy. FINDINGS: In the meta-analysis of 17 prospective observational studies (166 486 individuals; 9784 coronary heart disease events) a 1 SD higher urate concentration was associated with an odds ratio (OR) for coronary heart disease of 1·07 (95% CI 1·04-1·10). The corresponding OR estimates from the conventional, multivariable adjusted, and Egger Mendelian randomisation analysis (58 studies; 198 598 individuals; 65 877 events) were 1·18 (95% CI 1·08-1·29), 1·10 (1·00-1·22), and 1·05 (0·92-1·20), respectively, per 1 SD increment in plasma urate. INTERPRETATION: Conventional and multivariate Mendelian randomisation analysis implicates a causal role for urate in the development of coronary heart disease, but these estimates might be inflated by hidden pleiotropy. Egger Mendelian randomisation analysis, which accounts for pleiotropy but has less statistical power, suggests there might be no causal effect. These results might help investigators to determine the priority of trials of urate lowering for the prevention of coronary heart disease compared with other potential interventions. FUNDING: UK National Institute for Health Research, British Heart Foundation, and UK Medical Research Council

A Drosophila-centric view of protein tyrosine phosphatases

AbstractMost of our knowledge on protein tyrosine phosphatases (PTPs) is derived from human pathologies and mouse knockout models. These models largely correlate well with human disease phenotypes, but can be ambiguous due to compensatory mechanisms introduced by paralogous genes. Here we present the analysis of the PTP complement of the fruit fly and the complementary view that PTP studies in Drosophila will accelerate our understanding of PTPs in physiological and pathological conditions. With only 44 PTP genes, Drosophila represents a streamlined version of the human complement. Our integrated analysis places the Drosophila PTPs into evolutionary and functional contexts, thereby providing a platform for the exploitation of the fly for PTP research and the transfer of knowledge onto other model systems