Ceftazidime/Avibactam-Resistant Klebsiella pneumoniae subsp. pneumoniae Isolates in a Tertiary Italian Hospital: Identification of a New Mutation of the Carbapenemase Type 3 (KPC-3) Gene Conferring Ceftazidime/Avibactam Resistance

Several Klebsiella pneumoniae carpabenemase (KPC) gene mutations are associated with ceftazidime/avibactam (CAZ-AVI) resistance. Here, we describe four Klebsiella pneumoniae subsp. pneumoniae CAZ-AVI-resistant clinical isolates, collected at the University Hospital of Tor Vergata, Rome, Italy, from July 2019 to February 2020. These resistant strains were characterized as KPC-3, having the transition from cytosine to thymine (CAC-TAC) at nucleotide position 814, with histidine that replaces tyrosine (H272Y). In addition, two different types of KPC gene mutations were detected. The first one, common to three strains, was the D179Y (G532T), associated with CAZ-AVI resistance. The second mutation, found only in one strain, is a new mutation of the KPC-3 gene: a transversion from thymine to adenine (CTG-CAG) at nucleotide position 553. This mutation causes a KPC variant in which glutamine replaces leucine (Q168L). None of the isolates were detected by a rapid immunochromatographic assay for detection of carbapenemase (NG Biotech, Guipry, France) and were unable to grow on a selective chromogenic medium Carba SMART (bioMerieux, Firenze, Italy). Thus, they escaped common tests used for the prompt detection of Klebsiella pneumoniae KPC-producing.

Repetitive Suicidal Behaviors in a Case With a New Mutation of Wolfram Syndrome; A Jump From the Gene to The Behavior

Wolfram syndrome (WS) is a rare autosomal recessive neurodegenerative disease with variable symptoms including neuropsychiatric manifestations. A 26-year-old man was reported with classic symptoms of WS and repetitive psychiatric hospitalizations and at least 16 suicidal attempts. The genetic study demonstrated a novel homozygous stop-codon mutation on the WFS1 gene. This special type of mutation may be related to repetitive suicidal behaviors in this case of WS. Psychological support should be a routine practice in patients with WS.

A Novel KMT2D mutation in Kabuki syndrome with elevated liver enzymes and congenital bilateral hip dislocation

Kabuki syndrome (KS) is a rare syndrome that involves defects in a wide range of organs, with each organ showing a different severity of symptoms. Two genes have been associated with patients with KS: lysine (K)-specific demethylase 6A (KDM6A) and lysine (K)-specific methyltransferase 2D (KMT2D). The study reported the case of an 18-month-old Turkish boy diagnosed with KS. The patient showed a typical appearance: widely separated eyes, sparse eyebrows, long palpebral fissures, blue sclera, large prominent ears, and micrognathia. The patient was operated on because of bilateral hip dislocation and undescended testicles. He was also followed up by pediatric gastroenterology with asymptomatic liver enzyme elevation (AST- 79 U/L, ALT -68 U/L, ALP -52 U/L). The whole exome sequencing analysis revealed a novel pathogenic c.13285 C>T (p.Gln4429Ter) mutation in the KMT2D gene. The genotype-phenotype correlation of KS was not precisely established. As per our knowledge, there is limited literature which gives information about the hepato-biliary manifestations of KS. Here, we propose that the new mutation of the KMT2D gene may result in the typical facial features of KS with asymptomatic elevated liver enzymes.