Exome sequencing and identification of phenocopies in patients with clinically presumed hereditary nephropathies.

Rationale & Objective: Hereditary nephropathies are clinically and genetically heterogeneous disorders. For some patients, the clinical phenotype corresponds to a specific hereditary disease but genetic testing reveals that the expected genotype is not present (phenocopy). The aim of this study was to evaluate the spectrum and frequency of phenocopies identified by using exome sequencing in a cohort of patients who were clinically suspected to have hereditary kidney disorders.Study Design: Cross-sectional cohort study.Setting & Participants: 174 unrelated patients were recruited for exome sequencing and categorized into 7 disease groups according to their clinical presentation. They included autosomal dominant tubulointerstitial kidney disease, Alport syndrome, congenital anomalies of the kidney and urinary tract, ciliopathy, focal segmental glomerulosclerosis/steroid-resistant nephrotic syndrome, VACTERL association, and "other."Results: A genetic diagnosis (either likely pathogenic or pathogenic variant according to the guidelines of the American College of Medical Genetics) was established using exome sequencing in 52 of 174 (30%) cases. A phenocopy was identified for 10 of the 52 exome sequencing-solved cases (19%), representing 6% of the total cohort. The most frequent phenocopies (n = 5) were associated with genetic Alport syndrome presenting clinically as focal segmental glomerulosclerosis/steroidresistant nephrotic syndrome. Strictly targeted gene panels (<25 kilobases) did not identify any of the phenocopy cases.Limitations: The spectrum of described phenocopies is small. Selection bias may have altered the diagnostic yield within disease groups in our study population. The study cohort was predominantly of non-Finnish European descent, limiting generalizability. Certain hereditary kidney diseases cannot be diagnosed by using exome sequencing (eg, MUC1-autosomal dominant tubulointerstitial kidney disease).Conclusions: Phenocopies led to the recategorization of disease and altered clinical management. This study highlights that exome sequencing can detect otherwise occult genetic heterogeneity of kidney diseases

Sweden and informal language learning

This chapter focuses on informal language learning in Sweden. Sweden has a long tradition of teaching foreign languages in school, but formal language learning is currently in many ways being “challenged” by informal language learning. Research has shown how young people develop aspects of English proficiency thanks to extensive involvement in English‐mediated activities, such as: playing digital games in English, binge‐watching English‐speaking TV series or films, watching YouTube, or reading news via apps or social media. The term extramural English has been suggested for this learner‐initiated, generally voluntary, informal way of learning. While extramural English is very common, extramural Chinese, Japanese, and Korean are on the rise. The chapter begins by describing the case of Sweden, focusing on the current language situation and technological infrastructure, and then provides a survey of informal language learning in this small but linguistically diverse country

Poly[(μ4-phenyl­phospho­nato)zinc(II)]

The title two-dimensional coordination polymer, [Zn(C6H5PO3)] n , was synthesized serendipitously by reacting a tetraphosphonate cavitand Tiiii[C3H7, CH3, C6H5] and Zn(CH3COO)2·2H2O in a DMF/H2O mixture. The basic conditions of the reaction cleaved the phosphonate bridges at the upper rim of the cavitand, making them available for reaction with the zinc ions. The coordination polymer can be described as an inorganic layer in which zinc coordinates the oxygen atoms of the phosphonate groups in a distorted tetrahedral environment, while the phenyl groups, which are statistically disordered over two orientations, point up and down with respect to the layer. The layers interact through van der Waals interactions. The crystal studied was refined as a two-component twin