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

Cassina, Matteo; Cagnoli, Giulia; Zuccarello, Daniela; Gianantonio, Elena Di; Clementi, Maurizio

doi:10.1016/j.ejmg.2016.09.011

Cited by 21 publications

(14 citation statements)

References 156 publications

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“…In human, the loss of function mutations in DHODH causes Miller syndrome with a pattern of malformations similar to those observed in experimental animal studies,22 suggesting the teratogenic potential of leflunomide in human 23. The inhibitory effect of leflunomide on DHODH activity is species specific, and is 40 times stronger in rats than in human 3.…”

Section: Discussionsupporting

confidence: 55%

Leflunomide use during pregnancy and the risk of adverse pregnancy outcomes

et al. 2017

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Section: Discussionsupporting

confidence: 55%

Leflunomide use during pregnancy and the risk of adverse pregnancy outcomes

et al. 2017

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“…3A versus B), which in turn induces a rotation of the amino linker region by~40°, in addition to~0. 7 A shift of the amino linker toward M519 (Fig. 4B).…”

Section: Stereospecificity Of Chtsmentioning

confidence: 99%

“…However, the position of the c-carboxylate of the glutamate moiety of 1 versus 2 is different. 7 A shift of the amino linker toward M519 (Fig. In the case of ChTS with 2, the c-carboxylate extends to hydrogen bond with K284 ( Fig.…”

Section: Stereospecificity Of Chtsmentioning

confidence: 99%

“…While sharing identical chemical formula and atomic linkages, enantiomeric drugs are well known to display different pharmacological and toxicological effects [5]. For example S-thalidomide is a powerful teratogen, while its R-enantiomer was prescribed to pregnant women for lessening morning sickness [1,7]. Additionally, L-propoxyphene is an antitussive agent, while D-propoxyphene is an analgesic [8,9].…”

Section: Abstract: Chiral Recognition;mentioning

confidence: 99%

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Understanding the structural basis of species selective, stereospecific inhibition for Cryptosporidium and human thymidylate synthase

et al. 2019

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Thymidylate synthase (TS), found in all organisms, is an essential enzyme responsible for the de novo synthesis of deoxythymidine monophosphate. The TS active sites of the protozoal parasite Cryptosporidium hominis and human are relatively conserved. Evaluation of antifolate compound 1 and its R‐enantiomer 2 against both enzymes reveals divergent inhibitor selectivity and enzyme stereospecificity. To establish how C. hominis and human TS (ChTS and hTS) selectively discriminate 1 and 2, respectively, we determined crystal structures of ChTS complexed with 2 and hTS complexed with 1 or 2. Coupled with the previously determined structure of ChTS complexed with 1, we discuss a possible mechanism for enzyme stereospecificity and inhibitor selectivity.

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“…Of course, environmental influences can also cause vascular anomalies in embryos, these include exposure to drugs like phenytoin, cocaine and valproate [58][59][60]. Perhaps the most infamous are thalidomide and more recently, misoprostol.…”

Section: Drugs Taken During Pregnancy Leading To Vascular Disruption mentioning

confidence: 99%

Arterial dysgenesis and limb defects: Clinical and experimental examples

Vargesson

Hootnick

2017

Reproductive Toxicology

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Limb malformations are amongst the most common and visible birth effects. Causes have been purported to include genetic aberrations as well as teratogens, such as thalidomide. Here we review the evidence for vascular disruption in the genesis of limb malformations through abnormal arterial transitioning and from events such as amniocentesis, uterine constriction, and through teratogen exposure. We use several clinical and experimental examples and highlight the need to understand more about the role the vascular system plays in the molecular mechanisms underpinning normal limb development. AbstractLimb malformations are amongst the most common and visible birth effects. Causes have been purported to include genetic aberrations as well as teratogens, such as thalidomide. Here we review the evidence for vascular disruption in the genesis of limb malformations through abnormal arterial transitioning and from events such as amniocentesis, uterine constriction, and through teratogen exposure. We use several clinical and experimental examples and highlight the need to understand more about the role the vascular system plays in the molecular mechanisms underpinning normal limb development.

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

Cited by 21 publications

References 156 publications

Leflunomide use during pregnancy and the risk of adverse pregnancy outcomes

Leflunomide use during pregnancy and the risk of adverse pregnancy outcomes

Understanding the structural basis of species selective, stereospecific inhibition for Cryptosporidium and human thymidylate synthase

Arterial dysgenesis and limb defects: Clinical and experimental examples

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