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Genetic obesity: next-generation sequencing results of 1230 patients with obesity
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  • Published on:
    Comment on: Kleinendorst et al. Genetic obesity: next-generation sequencing results of 1230 patients with obesity. J Med Genet 2018 Sep;55(9):578-586.
    • Jean-Claude Chèvre, Postdoctoral fellow Inserm UMRS 954 N-GERE (Nutrition-Genetics-Environmental Risks), University de Lorraine, Faculty of Medicine, Nancy, France
    • Other Contributors:
      • Darlène Antoine, Doctoral student
      • Vivian Tam, Research assistant
      • Laurent Brunaud, Professor
      • Rosa-Maria Guéant-Rodriguez, Professor
      • Jean-Louis Guéant, Professor
      • David Meyre, Associate Professor

    To the Editor:
    We read with interest the article by Kleinendorst et al. on a next-generation sequencing-based gene panel analysis of 52 obesity-related genes in 1,230 patients with obesity [1]. This study is among the first to screen an exhaustive list of causal genes to determine the prevalence of monogenic obesity in a large series of severely obese children and adults recruited from a medical setting [2]. Genetic testing for obesity should be routinely performed in carefully selected patients, especially given the possibility of effective personalized treatments for a subset of monogenic cases [3]. We wanted to express several important concerns.
    First, the selection of these 52 genes is highly questionable. Several genes that have not been robustly associated with highly penetrant forms of obesity in the literature were included in the panel (e.g. IRS1, IRS2, IRS4, MCHR1), while 3 non-syndromic (MRAP2, KSR2, ADCY3) and 39 syndromic monogenic obesity genes were omitted [4,5].
    Second, the authors claim a ‘definitive diagnosis of a genetic obesity disorder’ in 3.9% of obese probands. This is a highly dubious conclusion considering that the authors used proprietary bioinformatics tools and did not detail how they classified variants as being pathogenic/likely pathogenic, uncertain, or likely begnin/begnin. In vitro functional characterization experiments are needed to confirm the pathogenicity of genetic variants [2].
    Third, the authors should have...

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    Conflict of Interest:
    None declared.