11. Hereditary angioedema due to C1-inhibitor deficiency in Macedonia : clinical characteristics, novel SERPING1 mutations, and genetic factors modifying the clinical phenotypeVesna Grivčeva-Panovska, Mitja Košnik, Peter Korošec, Slađana Andrejević, Ljerka Karadža-Lapić, Matija Rijavec, 2018, izvirni znanstveni članek Povzetek: Objective: Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a rare disease, characterized by swellings. We aimed to characterize on a clinical and molecular basis C1-INH-HAE patients in the Republic of Macedonia. Results: All 15 patients from six unrelated families were diagnosed with C1-INHHAE type I, with a mean age of symptom onset of 11 years and an average delay of diagnosis of 7 years. Patients reported on average 31 angioedema attacks/year, with a median clinical severity score (CSS) of 7. We identified three known mutations, and two mutations (c.813_818delCAACAA and c.1488T>G) were reported for the first time. To address the genotype-phenotype association, a pooled analysis including 78 C1-INH-HAE south-eastern European patients was performed, with additional analysis of F12-46C/T and KLKB1- 428G/A polymorphisms. We demonstrated that patients with nonsense and frameshift mutations, large deletions/insertions, splicing defects, and mutations at Arg444 exhibited an increased CSS compared with missense mutations, excluding mutations at Arg444. In addition, the CC F12-46C/T polymorphism was suggestive of earlier disease onset. Discussion: Genetic analysis helped identify the molecular basis of C1-INH-HAE given that causative mutations in SERPING1 were detected in all patients, including an infant before the appearance of clinical symptoms. We identified two novel mutations and further corroborated the genotype-phenotype relationship, wherein mutations with a clear effect on C1-INH function predispose patients to a more severe disease phenotype and CC F12-46C/T predisposes patients to earlier disease onset.
Ključne besede: hereditary angioedemas -- genetics -- Macedonia, C1 inhibitor, SERPING1 gene, C1 inhibitor, SERPING1 gene
Objavljeno v DiRROS: 30.11.2020; Ogledov: 1276; Prenosov: 281
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12. Multicenter evaluation of the fully automated PCR-based Idylla EGFR Mutation Assay on formalin-fixed, paraffin-embedded Q1 tissue of human lung cancerSolène M. Evrard, Estelle T. Clermont, Isabelle Rouquette, Samuel Murray, Sebastian Dintner, Yun-Chung Nam-Apostolopoulos, Beatriz Bellosillo, Mar V. Rodriguez, Ernest Nadal, Klaus H. Wiedorn, Mitja Rot, Izidor Kern, 2019, izvirni znanstveni članek Povzetek: Before initiating treatment of advanced nonesmall-cell lung cancer with tyrosine kinase inhibitors (eg, erlotinib, gefitinib, osimertinib, and afatinib), which inhibit the catalytic activity of epidermal growth factor receptor (EGFR), clinical guidelines require determining the EGFR mutational status for activating (EGFR exons 18, 19, 20, or 21) and resistance (EGFR exon 20) mutations. The EGFR resistance mutation T790M should be monitored at cancer progression. The Idylla EGFR Mutation Assay, performed on the Idylla molecular diagnostics platform, is a fully automated (<2.5 hours turnaround time) sample-to-result molecular test to qualitatively detect 51 EGFR oncogene point mutations, deletions, or insertions. In a 15- center evaluation, Idylla results on 449 archived formalin-fixed, paraffin-embedded tissue sections, originating from nonesmall-cell lung cancer biopsies and resection specimens, were compared with data obtained earlier with routine reference methods, including next-generation sequencing, Sanger sequencing, pyrosequencing, mass spectrometry, and PCR-based assays. When results were discordant, a third method of analysis was performed, when possible, to confirm test results. After confirmation testing and excluding invalids/errors and discordant results by design, a concordance of 97.6% was obtained between Idylla and routine test results. Even with <10 mm2 of tissue area, a valid Idylla result was obtained in 98.9% of the cases. The Idylla EGFR Mutation Assay enables sensitive detection of most relevant EGFR mutations in concordance with current guidelines, with minimal molecular expertise or infrastructure.
Ključne besede: non-small cell lung carconima -- diagnosis -- genetics, ErbB receptors, sequence analysis, tyrosine kinase inhibitors, epidermal growth factor receptor
Objavljeno v DiRROS: 07.10.2020; Ogledov: 1381; Prenosov: 981
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