RESUMEN
BACKGROUND: Long-QT syndrome is a monogenic disorder that produces cardiac arrhythmias and can lead to sudden death. At least 5 loci and 4 known genes exist in which mutations have been shown to be responsible for the disease. The potassium channel gene KCNQ1, previously named KVLQT1, on chromosome 11p15.5 is one of these. METHODS AND RESULTS: We initially analyzed one family using microsatellite markers and found linkage to KCNQ1. Mutation detection showed a G to C change in the last base of exon 6 (1032 G-->C) that does not alter the coded alanine. Restriction digest analysis in the family showed that only affected individuals carried the mutation. A previous report suggested that a G to A substitution at the same position may act as a splice mutation in KCNQ1, but no data was given to support this hypothesis nor was the transcription product identified. We have shown by reverse-transcription polymerase chain reaction that 2 smaller bands were produced for the KCNQ1 gene transcripts in addition to the normal-sized transcripts when lymphocytes of affected individuals were analyzed. Sequencing these transcripts showed a loss of exon 7 in one and exons 6 and 7 in the other, but an in-frame transcript was left in each instance. We examined other families in whom long-QT syndrome was diagnosed and found another unreported splice-site mutation, 922-1 G-->C, in the acceptor site of intron 5, and 2 of the previously reported 1032 G-->A mutations. All these showed a loss of exons 6 and 7 in the mutant transcripts, validating the proposal that a consensus sequence is affected in the exonic mutations and that the integrity of the base at position 1032 is essential for correct processing of the transcript. CONCLUSIONS: The 6 cases already reported in the literature with the 1032 G-->A transition, the novel 1032 G-->C transversion, and a recent G-->T transversion at the same base show that codon 344 is the second most frequently mutated after codon 341, suggesting at least two hotspots for mutations in KCNQ1.
Asunto(s)
ADN Recombinante/genética , Síndrome de QT Prolongado/genética , Mutación/genética , Canales de Potasio con Entrada de Voltaje , Canales de Potasio/genética , Preescolar , Codón/genética , Humanos , Canales de Potasio KCNQ , Canal de Potasio KCNQ1 , Masculino , Repeticiones de Microsatélite , Linaje , Sistemas de Lectura/genética , Transcripción GenéticaRESUMEN
Twenty-seven strains of coliforms (Enterobacteriaceae) isolated at Kisiizi Hospital, Uganda, were tested for their sensitivity to antibiotics. Sixteen of the 18 patient strains were identified as Escherichia coli, but biochemical analysis, serotyping, plasmid profile and antibiogram showed them to be heterogeneous. Resistance was very common to the antibiotics available in the community (ampicillin, chloramphenicol, tetracycline and trimethoprim), but was much less frequent for the agents used only in the hospital (gentamicin, ciprofloxacin and nitrofurantoin). A correlation was noted between the presence of large plasmids (150 kb or larger) and resistance to amoxicillin in patient strains of E. coli. The nine strains of coliform from the water supply were more heterogeneous and less resistant. The availability of antibiotics in the community seems linked to the development of multiresistant coliforms, which in a Ugandan context are very difficult to treat, and even more difficult to prevent.