Mutation update and uncommon phenotypes in a French cohort of 96 patients with WFS1-related disorders.

WFS1 mutations are responsible for Wolfram syndrome (WS) characterized by juvenile-onset diabetes mellitus and optic atrophy, and for low-frequency sensorineural hearing loss (LFSNHL). Our aim was to analyze the French cohort of 96 patients with WFS1-related disorders in order (i) to update clinical and molecular data with 37 novel affected individuals, (ii) to describe uncommon phenotypes and, (iii) to precise the frequency of large-scale rearrangements in WFS1. We performed quantitative polymerase chain reaction (PCR) in 13 patients, carrying only one heterozygous variant, to identify large-scale rearrangements in WFS1. Among the 37 novel patients, 15 carried 15 novel deleterious putative mutations, including one large deletion of 17,444 base pairs. The analysis of the cohort revealed unexpected phenotypes including (i) late-onset symptoms in 13.8% of patients with a probable autosomal recessive transmission; (ii) two siblings with recessive optic atrophy without diabetes mellitus and, (iii) six patients from four families with dominantly-inherited deafness and optic atrophy. We highlight the expanding spectrum of WFS1-related disorders and we show that, even if large deletions are rare events, they have to be searched in patients with classical WS carrying only one WFS1 mutation after sequencing.

Carbapenem-Resistant but Cephalosporin-Susceptible Pseudomonas aeruginosa in Urinary Tract Infections: Opportunity for Colistin Sparing.

This paper briefly reports the occurrence and epidemiology of carbapenem-resistant but cephalosporin-susceptible (Car-R/Ceph-S) Pseudomonas aeruginosa isolates from urinary tract infections (UTIs) in a tertiary-care hospital in the Southern Region of Hungary, and the phenotypic characterization of the possible resistance mechanisms in these isolates. Isolates and data were collected regarding P. aeruginosa UTIs corresponding to the period between 2008 and 2017. Susceptibility testing was performed using the Kirby-Bauer disk diffusion method; minimum inhibitory concentrations (MICs) of the isolates were determined using E-tests. The phenotypic detection of ampicillin C-type (AmpC) ß-lactamases, efflux pump overexpression and carbapenemase production was also performed. P. aeruginosa represented n = 575 (2.72% ± 0.64%) from outpatient, and n = 1045 (5.43% ± 0.81%) from inpatient urinary samples, respectively. Based on the disk diffusion test, n = 359 (22.16%) were carbapenem-resistant; in addition to carbapenems, n = (64.34%) were also resistant to ciprofloxacin; n = (60.17%) to gentamicin/tobramycin; n = (58.51%) to levofloxacin; and n = (27.57%) to amikacin. From among the carbapenem-resistant isolates, n = 56 (15.59%) isolates were multidrug-resistant, while n = 16 (4.46%) were extensively drug-resistant. From among the Car-R/Ceph-S isolates (n = 57), overexpression of AmpC was observed in n = 7 cases (12.28%); carbapenemase production in n = 4 (7.02%); while overexpression of efflux pumps was present in n = 31 (54.39%) isolates. To spare last-resort agents, e.g., colistin, the use of broad-spectrum cephalosporins or safe, alternative agents should be considered in these infections.