Phenotypic and genotypic spectrum of Turkish patients with isovaleric acidemia |
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| Affiliation: | 1. Hacettepe University, Faculty of Medicine, Department of Pediatrics, Metabolism Unit, Ankara, Turkey;2. Hacettepe University, Institute of Child Health, Ankara, Turkey;3. Aksaray University, Faculty of Science and Arts, Department of Biology, Aksaray, Turkey;4. Dr. Sami Ulus Maternity and Children Hospital, Training and Research Hospital, Division of Metabolism, Ankara, Turkey;5. Public Health Organisation of Turkey, Ankara, Turkey;6. Department of Pediatrics, Kirikkale University, Kirikkale, Turkey;1. Dept. of Biomedical Sciences, CRIBI Biotechnology Center, University of Padua, Italy;2. Dept. of Woman and Child Health, University of Padua, Italy;3. CNR Institute of Neuroscience, Padua, Italy;1. Department of Neurology, Children''s Hospital of Fudan University, Shanghai, China;2. Translational Research Center for Development and Disease, Children''s Hospital of Fudan University, Shanghai, China;1. Progenika Biopharma, Bizkaia, Spain;2. uniQure NV, Amsterdam, The Netherlands;3. Director of the German HITRIG, Third Medical Department and Policlinic, Giessen University Hospital, Justus-Liebig-University of Giessen, Giessen, Germany;4. Center for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Cologne, Germany;5. Institute of Clinical Chemistry, Lipid Clinic, Magdeburg, Germany;6. Charité—Universitätsmedizin Berlin, Berlin, Germany;7. Universitätsklinikum Carl Gustav Carus an der Technischen Universität, Medizinische Klinik III, Dresden, Germany;8. Institute of Clinical Chemistry and Laboratory Medicine and Lipid Outpatient Clinic, University Hospital Freiburg, Freiburg, Germany;9. Department of Vascular Medicine, Amsterdam Medical Center/University of Amsterdam, Amsterdam, The Netherlands;10. LMU Klinikum der Universität München, Medizinische Klinik und Poliklinik 4, München, Germany;11. Gießen and Marburg University Hospital, Giessen, Germany;12. Lipidambulanz, Rostock, Germany;13. Universitätsklinikum Münster, Medizinische Klinik D, Med. Clinic, Münster, Münster, Germany;14. Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;15. Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;p. Department of Medicine (Division of Medical Genetics), University of Washington, Seattle, WA, USA;q. Department of Genome Sciences, University of Washington, Seattle, WA, USA;r. Department of Medicine (Division of Metabolism, Endocrinology and Nutrition), University of Washington, Seattle, WA, USA |
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| Abstract: | We aim to investigate the genetic basis of isovaleryl-CoA dehydrogenase (IVD) gene mutations and genotype–phenotype correlations in Turkish patients. Accordingly, bi-directional sequencing was performed to screen 26 patients with isovaleric acidemia (IVA). Nine novels (c.145delC, c.234 + 3G > C, c.506_507insT, p.Glu85Gln, p.Met147Val, p.Ala268Val, p.Ile287Met, p.Gly346Asp and p.Arg382Trp) and six previously reported (c.456 + 2T > C, p.Arg21His, p.Arg21Pro, p.Arg363Cys, p.Arg363His p.Glu379Lys) pathogenic mutations were identified. Pathogenicity of the novel mutations was supported using computational programs. No clear genotype–phenotype correlation could be determined. One of the cases with the novel c.234 + 3G > C mutation has portoseptal liver fibrosis, the clinical condition that was first reported for IVA. This study is the first comprehensive report from Turkey related to IVA genetics that provides information about the high number of disease-causing novel mutations. |
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| Keywords: | Isovaleric acidemia Mutation screening Genotype–phenotype correlation |
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