RESUMO
Introduction: Pathogenic variants in TARS2 are associated with combined oxidative phosphorylation deficiency 21 (COXPD21), an autosomal recessive disorder usually presenting as mitochondrial encephalomyopathy. Kidney impairment has been documented in a minority of COXPD21 patients, mostly with distal renal tubular acidosis. Case report: We report on the first COXPD21 patient with generalized tubular dysfunction and early childhood progression to chronic kidney disease (CKD). Thorough diagnostic evaluation was initiated at six months of age due to failure to thrive, muscular hypotonia, motor delay and recurrent bronchiolitis. The boy was lost to follow-up until the age of two years, when he was readmitted with elevated creatinine level, reduced estimated glomerular filtrate rate, normochromic anaemia, metabolic acidosis and hyperkalaemia. Urine abnormalities pointed to generalized tubular dysfunction. Two novel heterozygous missense variants in TARS2 gene were detected by the means of whole exome sequencing: c.1298T>G (p.Phe438Cys) of maternal origin and c.1931A>T (p.Asp644Val) of paternal origin. Currently, at 4.5 years of age, the boy has failure to thrive, severe motor and verbal delay and end stage of CKD. We referred the patient to paediatric centre that provides renal replacement therapy. Conclusion: The overall clinical course in the patient we report on corresponds well to the previously reported cases of TARS2 related COXPD21, especially in regard to neurological and developmental aspects of the disease. However, we point out the generalized tubulopathy and early occurrence of CKD in our patient as atypical renal involvement in COXPD21. Additionally, this is the first report of hypothyroidism and hypoparathyroidism in a COXPD21 patient.
RESUMO
Teicoplanin resistance was transformed from a teicoplanin-resistant Staphylococcus aureus into the susceptible strain BB255 to give strain BB938. The cell wall composition, amidation of the iD-glutamate, and peptide crosslinking were identical in BB938 as in BB255 except for a 60% increased length of the glycan chain. Transductional crosses revealed that at least two distinct loci contributed in a cumulative fashion to teicoplanin resistance. One of these loci correlated with a mutation inactivating the anti-sigma factor RsbW. This mutation must have occurred during transformation and selection for teicoplanin resistance in BB938. Genetic manipulations involving the sigB operon showed that transcription factor SigB contributed to decreased teicoplanin susceptibility.
Assuntos
Antibacterianos/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/genética , Teicoplanina/farmacologia , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Western Blotting , Parede Celular/química , Mapeamento Cromossômico , DNA Bacteriano , Resistência Microbiana a Medicamentos/genética , Resistência a Múltiplos Medicamentos/genética , Humanos , Testes de Sensibilidade Microbiana , Óperon/genética , Peptidoglicano/análise , Pigmentos Biológicos/metabolismo , Ratos , Fator sigma/genética , Fator sigma/metabolismo , Transdução Genética , Transformação BacterianaRESUMO
From 1989 to 1995, 46 patients infected with the human immunodeficiency virus were diagnosed with tuberculosis at the University Hospital in Zurich. Using the IS6110 insertion sequence as a genetic marker, restriction fragment length polymorphism analyses were done for 52 Mycobacterium tuberculosis isolates. We have found a large degree of IS6110 polymorphism, ranging from 1 to 16 copies. For isolates from patients from whom multiple isolates had been available, the IS6110 pattern remained virtually stable over a period of up to 4 years, as well as during emerging drug resistance. In none of the cases was a reinfection of a patient with another strain detected. For isolates from 10 patients we detected identical patterns which could be associated with four clusters. In one of these, the strains exhibited a low IS6110 copy number (four bands), and the strains were further analyzed by hybridizing with (i) the polymorphic GC-rich repetitive sequence (PGRS) and (ii) the 36-bp direct-repeat (DR) cluster sequence. One of these isolates had a different pattern with the PGRS as well as with the DR sequence and could therefore be safely excluded from that cluster. These findings point to the importance of applying more than one genetic criterion in the molecular biological study of strain relatedness.
