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De Klein A; Riegman PH; Bijlsma EK; Heldoorn A; Muijtjens M; den Bakker MA; Avezaat CJ; Zwarthoff EC 《Human molecular genetics》1998,7(3):393-398
We describe a G-->A transition within intron 5 of the NF2 gene. This
mutation creates a consensus splice branch point sequence. To our knowledge
this is the first report of a mutation that creates a functional branch
point sequence in a human hereditary disorder. The new branch point
sequence is located 18 bp upstream of a consensus splice acceptor site. A
consensus splice donor site is found 106 bp 3' of the acceptor site. Asa
consequence the G-->A transition results in an alternatively spliced
mRNA containing an additional exon 5a of 106 bp derived from intron
sequences. We cloned the mutant cDNA and show that due to an in-frame stop
codon the cDNA codes for a truncated NF2 protein. The mutation was observed
in three affected members of an NF2 family. In a tumour of one of the
family members both alternatively spliced and wild-type mRNA were found,
although the wild-type allele of the gene is absent due to an interstitial
deletion on chromosome 22. We also show that immunoprecipitations reveal
the presence of full-length wild-type NF2 protein in the tumour lysate.
These data support the hypothesis that some degree of normal splicing of
the mutant precursor RNA is taking place. It is therefore likely that this
residual activity of the mutant allele explains the relatively mild
phenotype in the family. These data also indicate that complete
inactivation of the gene is not required for tumour formation.
相似文献
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Colorectal metastases to the liver: selective chemoembolization 总被引:6,自引:0,他引:6
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Sequelae of acute renal infections: CT evaluation 总被引:1,自引:0,他引:1
Seventeen patients with upper urinary tract infection who underwent 51 computed tomographic studies (two to five per patient; mean, three) were retrospectively evaluated. Five to 10 days after the initial examination, there was little change in parenchymal abnormalities, but perirenal inflammation worsened and then subsided over 2-8 weeks. Enlargement of the affected kidney, present initially in 12 patients, persisted up to 6 weeks and resolved by 10-16 weeks. Abnormalities of parenchymal contrast material enhancement persisted for 1-2 months. New cortical scars appeared in six of 12 patients with an initially normal renal contour and in one of five patients who had scars initially. Three patients with a renal abscess developed a new calyceal diverticulum, presumably by rupture of the abscess into the collecting system. The present study shows that abnormalities of renal size and enhancement persist for weeks to months after clinical signs of infection resolve and that scarring in adults with urinary tract infection occurs more frequently than was previously realized. 相似文献
50.
A prospective study of symptomatic bacteremia following platelet transfusion and of its management 总被引:6,自引:0,他引:6
EK Chiu ; KY Yuen ; AK Lie ; R Liang ; YL Lau ; AC Lee ; YL Kwong ; S Wong ; MH Ng ; TK Chan 《Transfusion》1994,34(11):950-954
BACKGROUND: The danger of bacteremia due to contaminated platelets is not well known. There are also no established guidelines for the management of febrile reactions after platelet transfusion. STUDY DESIGN AND METHODS: To determine the risk of symptomatic bacteremia after platelet transfusion, 3584 platelet transfusions given to 161 patients after bone marrow transplantation were prospectively studied. Platelet bags were routinely refrigerated for 24 hours after transfusion. Septic work-up was initiated for a temperature rise of more than 2 degrees C above the pretransfusion value within 24 hours of platelet transfusion or a temperature rise of more than 1 degree C that was associated with chills and rigor. Diagnosis of bacteremia after platelet transfusion was made only when the pairs of isolates from the blood and the platelet bags were identical with respect to their biochemical profile, antibiotic sensitivity, serotyping, or ribotyping. RESULTS: Thirty-seven febrile reactions, as defined above, occurred. Bacteremia subsequent to platelet transfusion was diagnosed in 10 cases. There was a 27-percent chance (95% CI, 15–43%) that these febrile reactions represented bacteremia that resulted from platelet transfusion. For a subgroup of 19 patients with a temperature rise of more than 2 degrees C, the risk of bacteremia was 42 percent (95% CI, 23–64%). Septic shock occurred in 4 of the 10 bacteremic patients. A rapid diagnosis was possible because the involved bacteria were demonstrated by direct Gram stain of the samples taken from the platelet bags of all 10 patients. CONCLUSION: Significant febrile reactions after platelet transfusion are highly likely to be indicative of bacteremia. Routine retention of platelet bags for subsequent microbiologic study was useful in the investigation of these febrile reactions. Empiric antibiotic therapy is indicated. 相似文献