Back to Search Start Over

Human teratogens and genetic phenocopies. Understanding pathogenesis through human genes mutation.

Authors :
Cassina, Matteo
Cagnoli, Giulia A.
Zuccarello, Daniela
Di Gianantonio, Elena
Clementi, Maurizio
Source :
European Journal of Medical Genetics. Jan2017, Vol. 60 Issue 1, p22-31. 10p.
Publication Year :
2017

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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
17697212
Volume :
60
Issue :
1
Database :
Academic Search Index
Journal :
European Journal of Medical Genetics
Publication Type :
Academic Journal
Accession number :
120473856
Full Text :
https://doi.org/10.1016/j.ejmg.2016.09.011