A dominant vimentin variant causes a rare syndrome with premature aging.

Autor: Cogné B; Centre Hospitalier Universitaire de Nantes, Service de Génétique Médicale, 9 quai Moncousu, 44093, Nantes, France.; Université de Nantes, CNRS, INSERM, l'institut du thorax, 44000, Nantes, France., Bouameur JE; Division of Cell and Developmental Biology, Institute of Biology, University of Leipzig, Philipp-Rosenthal-Strasse 55, 04103, Leipzig, Germany., Hayot G; Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France.; Centre National de la Recherche Scientifique, UMR7104, Illkirch, France.; Institut National de la Santé et de la Recherche Médicale, U1258, Illkirch, France.; Université de Strasbourg, Strasbourg, France., Latypova X; Centre Hospitalier Universitaire de Nantes, Service de Génétique Médicale, 9 quai Moncousu, 44093, Nantes, France.; Université de Nantes, CNRS, INSERM, l'institut du thorax, 44000, Nantes, France., Pattabiraman S; Department of Experimental Neurodegeneration, University Medical Center Göttingen, Walweg 33, 37073, Göttingen, Germany., Caillaud A; Université de Nantes, CNRS, INSERM, l'institut du thorax, 44000, Nantes, France., Si-Tayeb K; Université de Nantes, CNRS, INSERM, l'institut du thorax, 44000, Nantes, France., Besnard T; Centre Hospitalier Universitaire de Nantes, Service de Génétique Médicale, 9 quai Moncousu, 44093, Nantes, France.; Université de Nantes, CNRS, INSERM, l'institut du thorax, 44000, Nantes, France., Küry S; Centre Hospitalier Universitaire de Nantes, Service de Génétique Médicale, 9 quai Moncousu, 44093, Nantes, France.; Université de Nantes, CNRS, INSERM, l'institut du thorax, 44000, Nantes, France., Chariau C; Nantes Université, CHU Nantes, Inserm, CNRS, SFR Santé, FED 4203, Inserm UMS 016, CNRS UMS 3556, F-44000, Nantes, France., Gaignerie A; Nantes Université, CHU Nantes, Inserm, CNRS, SFR Santé, FED 4203, Inserm UMS 016, CNRS UMS 3556, F-44000, Nantes, France., David L; Nantes Université, CHU Nantes, Inserm, CNRS, SFR Santé, FED 4203, Inserm UMS 016, CNRS UMS 3556, F-44000, Nantes, France.; Nantes Université, CHU Nantes, Inserm, Centre de Recherche en Transplantation et Immunologie, UMR 1064, ITUN, F-44000, Nantes, France., Bordure P; Centre Hospitalier Universitaire de Nantes, Service Oto-rhino-laryngologie, 9 quai Moncousu, 44093, Nantes, France., Kaganovich D; Department of Experimental Neurodegeneration, University Medical Center Göttingen, Walweg 33, 37073, Göttingen, Germany.; 1 Base Pharmaceuticals, 9A Monument Square, #2A, Boston, MA, 02129, USA., Bézieau S; Centre Hospitalier Universitaire de Nantes, Service de Génétique Médicale, 9 quai Moncousu, 44093, Nantes, France.; Université de Nantes, CNRS, INSERM, l'institut du thorax, 44000, Nantes, France., Golzio C; Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France. christelle.golzio@igbmc.fr.; Centre National de la Recherche Scientifique, UMR7104, Illkirch, France. christelle.golzio@igbmc.fr.; Institut National de la Santé et de la Recherche Médicale, U1258, Illkirch, France. christelle.golzio@igbmc.fr.; Université de Strasbourg, Strasbourg, France. christelle.golzio@igbmc.fr., Magin TM; Division of Cell and Developmental Biology, Institute of Biology, University of Leipzig, Philipp-Rosenthal-Strasse 55, 04103, Leipzig, Germany. thomas.magin@uni-leipzig.de., Isidor B; Centre Hospitalier Universitaire de Nantes, Service de Génétique Médicale, 9 quai Moncousu, 44093, Nantes, France. bertrand.isidor@chu-nantes.fr.; Université de Nantes, CNRS, INSERM, l'institut du thorax, 44000, Nantes, France. bertrand.isidor@chu-nantes.fr.
Jazyk: angličtina
Zdroj: European journal of human genetics : EJHG [Eur J Hum Genet] 2020 Sep; Vol. 28 (9), pp. 1218-1230. Date of Electronic Publication: 2020 Feb 17.
DOI: 10.1038/s41431-020-0583-2
Abstrakt: Progeroid syndromes are a group of rare genetic disorders, which mimic natural aging. Unraveling the molecular defects in such conditions could impact our understanding of age-related syndromes such as Alzheimer's or cardiovascular diseases. Here we report a de novo heterozygous missense variant in the intermediate filament vimentin (c.1160 T > C; p.(Leu387Pro)) causing a multisystem disorder associated with frontonasal dysostosis and premature aging in a 39-year-old individual. Human vimentin p.(Leu387Pro) expression in zebrafish perturbed body fat distribution, and craniofacial and peripheral nervous system development. In addition, studies in patient-derived and transfected cells revealed that the variant affects vimentin turnover and its ability to form filaments in the absence of wild-type vimentin. Vimentin p.(Leu387Pro) expression diminished the amount of peripilin and reduced lipid accumulation in differentiating adipocytes, recapitulating key patient's features in vivo and in vitro. Our data highlight the function of vimentin during development and suggest its contribution to natural aging.
Databáze: MEDLINE
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