Читать книгу Genetic Disorders and the Fetus - Группа авторов - Страница 152

Disruption of imprinted genes, those differentially expressed depending on parental origin, has been investigated in FGR due to their important role in the placenta and in regulation of growth. Classic examples of the growth effects of imprinted genes in humans are the Beckwith–Wiedemann syndrome (BWS) and SRS that are associated with overgrowth and growth restriction, respectively.⁷⁹ BWS is caused by alterations of the 11p15.5 region, which includes at least eight imprinted genes organized into two domains. Growth restriction in SRS has been associated with epimutations leading to reduced IGF2 expression, as well as uniparental disomy and chromosomal rearrangements involving chromosome 7 including the MEST/PEG1 and/or the GRB10 regions.^{80, 81}

Reduced fetal growth has been associated with placental changes in DNA methylation at several imprinted differentially methylated regions (DMRs), including those associated with PLAGL1, PEG10, H19/IGF2, and ZNF331.^82–90 However, the reported changes in DNA methylation at imprinted DMRs have typically been of small magnitude and have not always been reproduced in other studies. Many studies have used SGA (<10th percentile) as a surrogate for FGR, a potential source of confusion, and many affected pregnancies deliver preterm or in association with PE, which could confound results. Furthermore, it is not clear if altered expression of imprinted genes is a cause of FGR or a compensatory effect of other defects. Larger sample sizes with stricter phenotypic criteria may help clarify the relationship between altered placental imprinting and FGR.