Two unusual cases of Gitelman's syndrome with a complex inheritance: how the phenotype can help interpret the genotype: lesson for the clinical nephrologist

Bartter\u2019s syndrome (BS) and Gitelman\u2019s syndrome (GS) are autosomal recessive disorders with overlapping features, caused by biallelic variants in six genes encoding proteins involved in renal electrolyte homeostasis in different districts of the nephron. Here we describe two patients with a clinical diagnosis of GS with a complex inheritance whose clinical interpretation and treatment proved challenging. In one patient, compound heterozygosity for two known pathogenic variant in the SLC12A3 gene was associated with an uncommon variant in the KCNJ1 gene (one of the known BS genes). The unusual severity of GS phenotype encountered in this patient led us to hypothesize that the missense variant can act as a genetic modifier by exacerbating the severity of the disease and by inducing BS-like clinical manifestations. In the other patient, two novel likely pathogenic variants in the SLC12A3 gene were coupled with a hitherto unreported rare variant in the SLC4A1 gene; the latter\u2019s disease-causing variants have been associated with both dominant and recessive forms of distal renal tubular acidosis (dRTA). Patient\u2019s medical history (he was clinically diagnosed with incomplete hypokalemic dRTA at 10 years old) supports the hypothesis of a dual molecular diagnosis and hence of a blended phenotype

Molecular characterization of paediatric glioneuronal tumours with neuropil-like islands: a genome-wide copy number analysis.

Paediatric glioneuronal tumour with neuropil-like islands (GTNI) is a rare neoplasm of neuronal differentiation and diffusely infiltrating astroglial and oligodendrocyte-like components. The 2007 World Health Organization classification of central nervous system tumours considered it as a pattern variation of anaplastic astrocytoma. There are few data on paediatric GTNI probably both for their rarity and variable clinical aggressiveness. We studied by SNP/CGH array four tumour samples of GTNI from two males and two females (one new-born and three children aged from 4 to 8 years), in order to identify any possible common genomic alteration. All patients received chemo- and radiotherapy after their surgical treatment. No genomic instability nor recurrent alterations have been demonstrated in two of our GTNI cases. In the remaining two, we detected a mosaic trisomy 8 (15-20%) in one case, and an amplification at 5q14.1 involving DMGDH (partially), BHMT2 and BHMT genes, with the distal breakpoint falling at 23 Kbp from the 5’UTR of JMY, a p53 cofactor. Although the smallness of the sample impairs any clinical-histological correlation, GTNI appear different at the molecular level, with genomic imbalances playing a possible role in at least part of them. Our work gives an important contribution in knowledge and classification of this family of tumours

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

L' impatto di una biblioteca storica: prima indagine sulla Biblioteca Palatina di Parma

Le biblioteche storiche e di conservazione da sempre sono viste come luoghi monumentali, di grande bellezza e pregio artistico. Il loro valore è noto a tutti, ma quanti conoscono davvero l’importanza che rivestono per la collettività? La qualificazione storica spesso tradisce una idea di staticità rivolta al passato, pochi si sono interrogati sul loro ruolo nella contemporaneità e sull’influenza che esercitano nella comunità scientifica e territoriale di riferimento. Partendo da questo presupposto, lo studio che qui si propone si è avvalso degli strumenti della ricerca qualitativa per indagare sull’impatto di una istituzione storica come la Biblioteca Palatina di Parma, attraverso le parole degli utenti, prima, e successivamente degli opinion leader. I risultati emersi mostrano la complessità di questo istituto, che rappresenta sì un luogo della memoria, scrigno di bellezza e di un patrimonio inestimabile, ma anche spazio di creazione, ispirazione e produzione, luogo di incontro e confronto professionale, di identità culturale con una forte vocazione territoriale, capace di influire sul benessere e sulla sfera emotiva, di aprire la mente e formare una cittadinanza attiva a consapevole