Human Mutation

Cover image for Vol. 35 Issue 12

Edited By: Richard G.H. Cotton and Garry R. Cutting

Impact Factor: 5.122

ISI Journal Citation Reports © Ranking: 2013: 25/165 (Genetics & Heredity)

Online ISSN: 1098-1004

Featured

  • TP53 Mutation Analysis in Clinical Practice: Lessons From Chronic Lymphocytic Leukemia

    TP53 Mutation Analysis in Clinical Practice: Lessons From Chronic Lymphocytic Leukemia

    In Chronic lymphocytic leukemia, TP53 defects associate with impaired survival and therapy resistance. Here we describe the biological and clinical consequences of TP53 dysfunction as well as the methodical aspects of TP53 analysis including next generation sequencing. We also discuss the mechanisms of TP53 defects' clonal evolution mainly with respect to their selection by therapy.

  • Molecular Analysis, Pathogenic Mechanisms, and Readthrough Therapy on a Large Cohort of Kabuki Syndrome Patients

    Molecular Analysis, Pathogenic Mechanisms, and Readthrough Therapy on a Large Cohort of Kabuki Syndrome Patients

    In this report, we have expanded the spectrum of mutations of KMT2D and KDM6A genes by analysing our cohort of 303 Kabuki patients by direct sequencing, MLPA and quantitative PCR. Based on KMT2D biological role, we designed functional studies that highlighted the haploinsufficiency of KMT2D as one of the mechanisms underlying the pathogenesis of the disease. Moreover, we provided the first preliminary proof-of-concept that occurring nonsense mutations in KMT2D and KDM6A can be effectively suppressed and the functional endogenous protein level and biological activity of KMT2D and KDM6A proteins restored.

  • Identification of a Novel 5′ Alternative CFTR mRNA Isoform in a Patient with Nasal Polyposis and CFTR Mutations

    Identification of a Novel 5′ Alternative CFTR mRNA Isoform in a Patient with Nasal Polyposis and CFTR Mutations

    A novel 5' alternative CFTR transcript was identified in a 12y-old patient presenting with isolated nasal polyposis and being heterozygous for c.2551C>T (p.Arg851*). Its characterization was made after identification of the c.-2954G>A mutation which was shown to enhance promoter activity. The novel, presumably non-functional, transcript could represent a novel molecular CFTR defect associated with CFTR-related disorders.

  • Locus-Specific Databases in Cancer: What Future in a Post-Genomic Era? The TP53 LSDB paradigm

    Locus-Specific Databases in Cancer: What Future in a Post-Genomic Era? The TP53 LSDB paradigm

    The discovery of a novel gene lead to the discovery phase with an immediate increase in the number of studies leading to the identification of novel mutants (blue line) and mutant diversity rises quickly (green line). This is associated with a high frequency of published reports (red line) in high ranking journals (black line). During the consolidation phase, mutant diversity reaches a plateau the number of mutation reports drops with a decrease in publication quality and an increase in inconsistent reports (brown lines). The application phase will begin only if the gene has clinical value.

  • TP53 Mutants in the Tower of Babel of Cancer Progression

    TP53 Mutants in the Tower of Babel of Cancer Progression

    We review studies investigating TP53 mutations for their effect on the capacity of this protein to act as a transcription factor. We also review recent findings on how TP53 mutants can exhibit gain-of-function properties. Somatic as well as germline TP53 mutations are considered, and the possibilities to stratify patients based on the features of P53 mutant proteins are discussed. In the analogy with the Tower of Babel, the different languages stand for the staggering functional heterogeneity of P53 mutants associated with cancer.

  • TP53 Mutation Analysis in Clinical Practice: Lessons From Chronic Lymphocytic Leukemia
  • Molecular Analysis, Pathogenic Mechanisms, and Readthrough Therapy on a Large Cohort of Kabuki Syndrome Patients
  • Identification of a Novel 5′ Alternative CFTR mRNA Isoform in a Patient with Nasal Polyposis and CFTR Mutations
  • Locus-Specific Databases in Cancer: What Future in a Post-Genomic Era? The TP53 LSDB paradigm
  • TP53 Mutants in the Tower of Babel of Cancer Progression

New Video Highlight

View More Video Highlights

New video highlight created by Daman Kumari and Kristen Moulton on their recently published Human Mutation paper entitled, "Identification of Fragile X Syndrome-Specific Molecular Markers in Human Fibroblasts: A Useful Model to Test the Efficacy of Therapeutic Drugs."

New Virtual Issue

Please see the new Virtual Issue, "Recommendations and Standards for the Reporting and Databasing of Genetic Variations", guest edited by Johan den Dunnen and Mauno Vihinen. Articles in this Virtual Issue have been made freely available online.

See also this valuable Virtual Issue on assessing pathogenicity of gene variants – also free online

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