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  1. Fulltext The Risk of Congenital Heart Anomalies Following Prenatal Exposure to Serotonin Reuptake Inhibitors-Is Pharmacogenetics the Key?
    Daud AN, Bergman JE, Kerstjens-Frederikse WS, Groen H, Wilffert B
    Int J Mol Sci, 2016 Aug 13;17(8).
    PMID: 27529241 DOI: 10.3390/ijms17081333
    Serotonin reuptake inhibitors (SRIs) are often prescribed during pregnancy. Previous studies that found an increased risk of congenital anomalies, particularly congenital heart anomalies (CHA), with SRI use during pregnancy have created concern among pregnant women and healthcare professionals about the safety of these drugs. However, subsequent studies have reported conflicting results on the association between CHA and SRI use during pregnancy. These discrepancies in the risk estimates can potentially be explained by genetic differences among exposed individuals. In this review, we explore the potential pharmacogenetic predictors involved in the pharmacokinetics and mechanism of action of SRIs, and their relation to the risk of CHA. In general, the risk is dependent on the maternal concentration of SRIs and the foetal serotonin level/effect, which can be modulated by the alteration in the expression and/or function of the metabolic enzymes, transporter proteins and serotonin receptors involved in the serotonin signalling of the foetal heart development. Pharmacogenetics might be the key to understanding why some children exposed to SRIs develop a congenital heart anomaly and others do not.
    Matched MeSH terms: Heart Defects, Congenital/genetics*
  2. Fulltext Prenatal exposure to serotonin reuptake inhibitors and congenital heart anomalies: an exploratory pharmacogenetics study
    Daud ANA, Bergman JEH, Kerstjens-Frederikse WS, van der Vlies P, Hak E, Berger RMF, et al.
    Pharmacogenomics, 2017 Jul;18(10):987-1001.
    PMID: 28639488 DOI: 10.2217/pgs-2017-0036
    AIM: To explore the role of pharmacogenetics in determining the risk of congenital heart anomalies (CHA) with prenatal use of serotonin reuptake inhibitors.

    METHODS: We included 33 case-mother dyads and 2 mother-only (child deceased) cases of CHA in a case-only study. Ten genes important in determining fetal exposure to serotonin reuptake inhibitors were examined: CYP1A2, CYP2C9, CYP2C19, CYP2D6, ABCB1, SLC6A4, HTR1A, HTR1B, HTR2A and HTR3B.

    RESULTS: Among the exposed cases, polymorphisms that tended to be associated with an increased risk of CHA were SLC6A4 5-HTTLPR and 5-HTTVNTR, HTR1A rs1364043, HTR1B rs6296 and rs6298 and HTR3B rs1176744, but none reached statistical significance due to our limited sample sizes.

    CONCLUSION: We identified several polymorphisms that might potentially affect the risk of CHA among exposed fetuses, which warrants further investigation.

    Matched MeSH terms: Heart Defects, Congenital/genetics
  3. Fulltext 22q11.2 deletion syndrome in diverse populations
    Kruszka P, Addissie YA, McGinn DE, Porras AR, Biggs E, Share M, et al.
    Am J Med Genet A, 2017 Apr;173(4):879-888.
    PMID: 28328118 DOI: 10.1002/ajmg.a.38199
    22q11.2 deletion syndrome (22q11.2 DS) is the most common microdeletion syndrome and is underdiagnosed in diverse populations. This syndrome has a variable phenotype and affects multiple systems, making early recognition imperative. In this study, individuals from diverse populations with 22q11.2 DS were evaluated clinically and by facial analysis technology. Clinical information from 106 individuals and images from 101 were collected from individuals with 22q11.2 DS from 11 countries; average age was 11.7 and 47% were male. Individuals were grouped into categories of African descent (African), Asian, and Latin American. We found that the phenotype of 22q11.2 DS varied across population groups. Only two findings, congenital heart disease and learning problems, were found in greater than 50% of participants. When comparing the clinical features of 22q11.2 DS in each population, the proportion of individuals within each clinical category was statistically different except for learning problems and ear anomalies (P 
    Matched MeSH terms: Heart Defects, Congenital/genetics
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