title: Human teratogens and genetic phenocopies. Understanding pathogenesis through human genes mutation.
abstract: Exposure to teratogenic drugs during pregnancy is associated with a wide range of embryo-fetal anomalies and sometimes results in recurrent and recognizable patterns of malformations; however, the comprehension of the mechanisms underlying the pathogenesis of drug-induced birth defects is difficult, since teratogenesis is a multifactorial process which is always the result of a complex interaction between several environmental factors and the genetic background of both the mother and the fetus. Animal models have been extensively used to assess the teratogenic potential of pharmacological agents and to study their teratogenic mechanisms; however, a still open issue concerns how the information gained through animal models can be translated to humans. Instead, significant information can be obtained by the identification and analysis of human genetic syndromes characterized by clinical features overlapping with those observed in drug-induced embryopathies. Until now, genetic phenocopies have been reported for the embryopathies/fetopathies associated with prenatal exposure to warfarin, leflunomide, mycophenolate mofetil, fluconazole, thalidomide and ACE inhibitors. In most cases, genetic phenocopies are caused by mutations in genes encoding for the main targets of teratogens or for proteins belonging to the same molecular pathways. The aim of this paper is to review the proposed teratogenic mechanisms of these drugs, by the analysis of human monogenic disorders and their molecular pathogenesis.
authors.affiliation: Clinical Genetics Unit, Department of Women's and Children's Health, University of Padova, Padova, Italy. Electronic address: matteo.cassina@unipd.it.
authors.forename: Matteo
authors.initials: M
authors.lastname: Cassina
authors.affiliation: Clinical Genetics Unit, Department of Women's and Children's Health, University of Padova, Padova, Italy.
authors.forename: Giulia A
authors.initials: GA
authors.lastname: Cagnoli
authors.affiliation: Clinical Genetics Unit, Department of Women's and Children's Health, University of Padova, Padova, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Zuccarello
authors.affiliation: Clinical Genetics Unit, Department of Women's and Children's Health, University of Padova, Padova, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Di Gianantonio
authors.affiliation: Clinical Genetics Unit, Department of Women's and Children's Health, University of Padova, Padova, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Clementi
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000453:epidemiology / Q000473:pathology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects; D000818:Animals; D005260:Female; D005315:Fetal Diseases / Q000139:chemically induced / Q000453:epidemiology / Q000473:pathology*; D005333:Fetus / Q000187:drug effects / Q000473:pathology; D015725:Fluconazole / Q000009:adverse effects; D006801:Humans; D007555:Isoxazoles / Q000009:adverse effects; D000077339:Leflunomide; D009154:Mutation; D009173:Mycophenolic Acid / Q000009:adverse effects; D010641:Phenotype; D011247:Pregnancy; D064793:Teratogenesis / Q000187:drug effects*; D013723:Teratogens; D013792:Thalidomide / Q000009:adverse effects; D014859:Warfarin / Q000009:adverse effects
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D007555:Isoxazoles; D013723:Teratogens; D013792:Thalidomide; D014859:Warfarin; D015725:Fluconazole; D000077339:Leflunomide; D009173:Mycophenolic Acid
keywords: Birth defect; Genetics; Malformation; Phenocopy; Syndrome; Teratogen