Evaluation of DHPLC analysis in mutational scanning of Notch3, a gene with a high G-C content.

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  • Additional Information
    • Source:
      Publisher: Wiley-Liss Country of Publication: United States NLM ID: 9215429 Publication Model: Print Cited Medium: Internet ISSN: 1098-1004 (Electronic) Linking ISSN: 10597794 NLM ISO Abbreviation: Hum Mutat Subsets: MEDLINE
    • Publication Information:
      Original Publication: New York : Wiley-Liss, c1992-
    • Subject Terms:
      Receptors, Cell Surface*; Chromatography, High Pressure Liquid/*methods ; Cytosine/*analysis ; DNA Mutational Analysis/*methods ; Guanine/*analysis ; Proto-Oncogene Proteins/*genetics; Base Composition ; Dementia, Multi-Infarct/epidemiology ; Dementia, Multi-Infarct/genetics ; Humans ; Mutation ; Nucleic Acid Denaturation ; Nucleic Acid Heteroduplexes/genetics ; Polymorphism, Single-Stranded Conformational ; Receptor, Notch3 ; Receptors, Notch ; Reproducibility of Results ; Sensitivity and Specificity
    • Abstract:
      Notch3 mutations cause CADASIL, an increasingly recognized cause of subcortical ischemic stroke and vascular dementia in human adults. In the absence of any specific diagnostic criteria, CADASIL diagnosis is based on mutational scanning of Notch3, which is a large gene composed of 33 exons with a high G-C content. In this study we examined the sensitivity of denaturing high performance liquid chromatography (DHPLC). First we established the theoretical optimal parameters, then we examined a large collection of amplicons in which we had previously identified distinct pathogenic mutations or polymorphisms. We further performed Notch3 mutational scanning in five patients suspected of CADASIL diagnosis in which previous scanning, including SSCP and heteroduplexes analysis, failed to detect any pathogenic mutation. DHPLC resolved 97% of mutations previously detected by sequencing and allowed identification of two novel pathogenic mutations: R607C and F984C. These data indicate that DHPLC is a sensitive screening method particularly suitable for epidemio-genetic screening of CADASIL.
      (Copyright 2000 Wiley-Liss, Inc.)
    • Accession Number:
      0 (NOTCH3 protein, human)
      0 (Nucleic Acid Heteroduplexes)
      0 (Proto-Oncogene Proteins)
      0 (Receptor, Notch3)
      0 (Receptors, Cell Surface)
      0 (Receptors, Notch)
      5Z93L87A1R (Guanine)
      8J337D1HZY (Cytosine)
    • Publication Date:
      Date Created: 20000111 Date Completed: 20010111 Latest Revision: 20161124
    • Publication Date:
      20231215
    • Accession Number:
      10.1002/1098-1004(200012)16:6<518::AID-HUMU9>3.0.CO;2-Q
    • Accession Number:
      11102981