RESUMEN
Congenital disorder of glycosylation type Ig (ALG12-CDG) is a rare inherited metabolic disease caused by a defect in alpha-mannosyltransferase 8, encoded by the ALG12 gene (22q13.33). To date, only 15 patients have been diagnosed with ALG12-CDG globally. Due to a newborn Slovak patient's clinical and biochemical abnormalities, the isoelectric focusing of transferrin was performed with observed significant hypoglycosylation typical of CDG I. Furthermore, analysis of neutral serum N-glycans by mass spectrometry revealed the accumulation of GlcNAc2Man5-7 and decreased levels of GlcNAc2Man8-9, which indicated impaired ALG12 enzymatic activity. Genetic analysis of the coding regions of the ALG12 gene of the patient revealed a novel homozygous substitution mutation c.1439T>C p.(Leu480Pro) within Exon 10. Furthermore, both of the patient's parents and his twin sister were asymptomatic heterozygous carriers of the variant. This comprehensive genomic and glycomic approach led to the confirmation of the ALG12 pathogenic variant responsible for the clinical manifestation of the disorder in the patient described.
Asunto(s)
Trastornos Congénitos de Glicosilación/genética , Predisposición Genética a la Enfermedad , Manosiltransferasas/genética , Polisacáridos/genética , Trastornos Congénitos de Glicosilación/epidemiología , Trastornos Congénitos de Glicosilación/patología , Femenino , Pruebas Genéticas , Glicosilación , Homocigoto , Humanos , Lactante , Recién Nacido , Masculino , Mutación Missense/genética , Fenotipo , Polisacáridos/metabolismo , Eslovaquia/epidemiología , Transferrina/genéticaRESUMEN
This study aimed to evaluate the potential pathogenicity and antibiotic resistance of 31 environmental Vibrio isolates obtained from surface water in southern and eastern Slovakia. Isolates were identified as Vibrio cholerae non-O1/non-O139 and Vibrio metschnikovii by biochemical tests, MALDI biotyping, and 16S RNA gene sequencing. Analysis of the susceptibility to 13 antibacterial agents showed susceptibility of all isolates to ciprofloxacin, trimethoprim/sulfamethoxazole, chloramphenicol, gentamicin, imipenem, tetracyclin, and doxycycline. We recorded high rates of resistance to ß-lactams and streptomycin. Investigation of antibiotic resistance showed five different antibiotic profiles with resistance to antibacterials from three classes, but no multidrug resistance was observed. The investigation of the pathogenic potential of V. cholerae isolates showed that neither the cholera toxin coding gene ctxA nor the genes zot (zonula occludens toxin), ace (accessory cholera toxin), and tcpA (toxin-coregulated pilus) were present in any of 31 isolated samples. Gene ompU (outer membrane protein) was confirmed in 80% and central regulatory protein-coding gene toxR in 71% of V. cholerae isolates, respectively. A high prevalence of the hemolysin coding gene hlyA in all V. cholerae was observed. The data point toward the importance of systematic monitoring and comparative studies of potentially pathogenic vibrios in European countries.
