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Imprinting Disorders of Early Childhood

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Epigenetic Epidemiology

Abstract

Imprinted genes are exceptional in that one allele is silenced (imprinted) in a parent of origin specific manner, making the two parental alleles functionally different. Imprinted genes are known to play a vital role in fetal growth and normal metabolism and most of the medical conditions caused by aberrant imprinting result in problems with growth, neurodevelopment and glycaemic control. There are eight known human disorders; Beckwith Wiedemann syndrome (fetal overgrowth, umbilical abnormalities and macroglossia), Silver Russell Syndrome (poor fetal and post natal growth and short stature), Prader Willi syndrome (hypotonia, developmental delay, excessive appetite and obesity), Angelman syndrome (severe developmental delay, no speech and ataxia), Transient Neonatal Diabetes (neonatal diabetes and low birth weight), Temple syndrome (hypotonia short stature and early puberty), Wang syndrome (hypotonia, developmental delay and small thorax) and Pseudohypoparathyroidism type 1B (hypoparathyroidism). At any of the imprinted loci involved in these conditions, abnormal gene expression is due to three mechanisms: epigenetic loss or gain of DNA methylation within control regions, uniparental disomy and structural chromosome abnormalities. The known prevalence of each condition depends on the distinctiveness of symptoms and thus ease of diagnosis and the susceptibility of the different loci to genetic and epigenetic aberrations; the reasons for the difference in susceptibility at different loci is not yet known. This chapter describes the imprinted loci and the medical consequences of aberrant imprinted gene expression.

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Abbreviations

AS:

Angelman syndrome

BWS:

Beckwith Wiedemann syndrome

DMR:

Differentially methylated region

ICR:

Imprinting control region

PHP1B:

Pseudohypoparathyroidism type 1B

PWS:

Prader Willi syndrome

SDS:

Standard deviation scores

SRS:

Silver Russell syndrome

TND:

Transient Neonatal Diabetes

TS:

Temple syndrome

WS:

Wang syndrome

UPD:

Uniparental disomy

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Authors and Affiliations

  1. Division of Human Genetics, Faculty of Medicine, University of Southampton, Southampton, UK

    I. Karen Temple & Deborah J. G. Mackay

  2. Genetic Medicine, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK

    Jill Clayton-Smith

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  1. I. Karen Temple
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  2. Jill Clayton-Smith
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  3. Deborah J. G. Mackay
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Correspondence to I. Karen Temple .

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  1. , Obstetrics and Gynecology Epidemiology D, Brigham and Women’s Hospital, Longwood Avenue 221, Boston, 02115, Massachusetts, USA

    Karin B. Michels

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Temple, I.K., Clayton-Smith, J., Mackay, D.J.G. (2012). Imprinting Disorders of Early Childhood. In: Michels, K. (eds) Epigenetic Epidemiology. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2495-2_9

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