UPD Related Syndromes Caused by Imprinting
UPD-related syndromes caused by imprinting include paternal UPD(6) syndrome (transient neonatal diabetes = TNDM), maternal UPD(7) and maternal UPD(11) syndrome (Silver-Russell syndrome = SRS), paternal UPD 11 and paternal UPD 7 syndrome (Beckwith-Wiedeman
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UPD Related Syndromes Caused by Imprinting
Abstract UPD-related syndromes caused by imprinting include paternal UPD(6) syndrome (transient neonatal diabetes = TNDM), maternal UPD(7) and maternal UPD(11) syndrome (Silver-Russell syndrome = SRS), paternal UPD 11 and paternal UPD 7 syndrome (Beckwith-Wiedemann-syndrome = BWS), maternal UPD 14 syndrome (Temple syndrome = TS), paternal UPD 14 syndrome (Kagami syndrome = KS), maternal UPD 15 syndrome (Prader-Willi syndrome = PWS), paternal UPD 15 syndrome (Angelman syndrome = AS), and paternal UPD 20 syndrome (pseudohypoparathyroidism type Ib = PHP-Ib). In addition, 10 personal reports on experiences of families or patients with UPD- or imprinting-related diseases are provided, including how they obtained the diagnosis and what it means to live with the disease. In most cases, it is not important if both chromosomes come from one parent or if both parents provide one copy each.1 For chromosomes 6, 11, 14, 15, and 20, the situation is different. As shown schematically in Fig. 1.3a, these chromosomes obtain a divergent ‘‘stamp’’—an imprint dependent on whether the chromosome underwent male or female gametogenesis. The biological basis for this imprint is the methylation of DNA, as depicted in Fig. 4.1. Methylation is most important in the promoter regions of the imprinted genes and suppresses gene expression. Chromatin structure changes and the posttranslational histone modification can be the result of DNA methylation, as well (Eggermann 2009). Note that disorders with known imprinting centers (i.e. the promoter regions of differentially methylated genes) have an enhanced risk of developing when assisted reproduction technologies are applied in elderly putative parents (Sect. 3.3.3). The main topic of this book is UPD. Obviously, iUPD, hUPD, and h/iUPD may lead to the simultaneous presence of identically imprinted DNA stretches. In addition, the deletion of one imprinted region does not only reduces the gene dosage of the corresponding region; at the same time, UPD is mimicked, with a lack of one parental allele and thus exclusive expression of the other parental 1
Because imprinting is the topic of this chapter, recessive point mutations are not included. Rather, they are just treated as rare exceptions in this chapter; for more details, see Chaps. 5–7.
T. Liehr, Uniparental Disomy (UPD) in Clinical Genetics, DOI: 10.1007/978-3-642-55288-5_4, Springer-Verlag Berlin Heidelberg 2014
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UPD Related Syndromes Caused by Imprinting
Fig. 4.1 Epigenetic modification of DNA is usually equivalent to methylation of cytosines along a DNA strand. Here, such a DNA part is shown when it passes through replication and postreplication methylation
allele. The biological result for the cell is (almost) the same. Schinzel (2001) included such cases in the UPD-related disorder group. Finally, the same effect as in microdeletion of an imprinted region can be present due to duplications, point mutations in the so-called imprinting center, or epigenetic mutations (Fig. 4.2). Am
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