ABSTRACT
To estimate the contribution of single and multi-exon NF1 gene copy-number changes to the NF1 mutation spectrum, we analysed a series of 201 Italian patients with neurofibromatosis type 1 (NF1). Of these, 138 had previously been found, using denaturing high-performance liquid chromatography or protein truncation test, to be heterozygous for intragenic NF1 point mutations/deletions/insertions, and were excluded from this analysis. The remaining 63 patients were analysed using multiplex ligation-dependent probe amplification (MLPA), which allows detection of deletions or duplications encompassing >or=1 NF1 exons, as well as entire gene deletions. MLPA results were validated using real-time quantitative PCR (qPCR) or fluorescent in situ hybridisation. MLPA screening followed by real-time qPCR detected a total of 23 deletions. Of these deletions, six were single exon, eight were multi-exon, and nine were of the entire NF1 gene. In our series, deletions encompassing >or=1 NF1 exons accounted for approximately 7% (14/201) of the NF1 gene mutation spectrum, suggesting that screening for these should now be systematically included in genetic testing of patients with NF1.
Subject(s)
Exons/genetics , Gene Deletion , Gene Dosage , Genes, Neurofibromatosis 1 , Neurofibromatosis 1/genetics , Adolescent , Adult , Child , Child, Preschool , Cohort Studies , Computer Systems , Female , Humans , In Situ Hybridization, Fluorescence , Infant , Italy/epidemiology , Male , Middle Aged , Neurofibromatosis 1/epidemiology , Neurofibromatosis 1/pathology , Nucleic Acid Amplification Techniques , Phenotype , Polymerase Chain Reaction/methods , Scoliosis/epidemiology , Scoliosis/geneticsABSTRACT
UNLABELLED: To assess the role of transesophageal pacing (TP) at very high rates in the follow-up of patients with recurrent and sustained paroxysmal atrial fibrillation (AF) on therapy, the authors studied 15 patients (10 women, 5 men; aged forty-four to seventy-seven years old). Of them only 1 had a mild mitral regurgitation; none had hyperthyroidism or acute ischemic heart disease. They tested propafenone (P) at a dose of 1.4-2 mg/kg over ten minutes as an intravenous bolus and 0.5 mg/minute as intravenous maintenance for two hours and then 300 mg twice daily orally and chronically. Serial TPs at very rapid rates (up to 600 bpm) were performed to test the long-term efficacy of P to prevent paroxysmal AF. The mean follow-up was fifteen months (nine to twenty-four months). RESULTS: Intravenous P converted AF in five to ninety minutes (mean twenty-one minutes) in 9/15 patients (conversion rate of 60%); in an additional 4 patients oral P converted AF in two to fifteen hours. In the other 2 patients P failed to convert AF. Three patients experienced recurrence of AF in the early follow-up. Of the 10 patients who completed the entire protocol, only 1, who had mild mitral prolapse regurgitation and AF induction by TP, experienced new episodes of AF during follow-up. No significant side effects were noted during P therapy. CONCLUSIONS: Propafenone appears safe and effective for controlling and preventing recurrent and sustained AF. Transesophageal pacing is a valid tool for predicting the efficacy of long-term therapy in the follow-up of patients with paroxysmal atrial fibrillation.
