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Lookup NU author(s): Dr Miranda Splitt
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The imprinted expression of the IGF2 and H19 genes is controlled by the imprinting control region 1 (ICR1) located at chromosome 11p15.5. DNA methylation defects involving ICR1 result in two growth disorders with opposite phenotypes: an overgrowth disorder, the Beckwith-Wiedemann syndrome (maternal ICR1 hypermethylation in 10% of BWS cases) and a growth retardation disorder, the Silver-Russell syndrome (paternal ICR1 loss of methylation in 60% of SRS cases). In familial BWS, hypermethylation of ICR1 has been found in association with microdeletion of repetitive DNA motifs within ICR1 that bind the zinc finger protein CTCF; but more recently, ICR1 point mutations were described in BWS pedigrees. We present a case report of two brothers with BWS and prolonged post-pubertal growth resulting in very large stature. A maternally inherited point mutation was identified in ICR1 in both brothers, which altered binding of OCT transcription factors. The same mutation was present on the paternally inherited allele of their unaffected mother. This is a second report of a point mutation causing ICR1 hypermethylation by altering an OCT-binding motif. The atypical growth phenotype of the brothers may be connected to the unusual underlying cause of their BWS. European Journal of Human Genetics (2012) 20, 240-243; doi:10.1038/ejhg.2011.166; published online 24 August 2011
Author(s): Poole RL, Leith DJ, Docherty LE, Shmela ME, Gicquel C, Splitt M, Temple K, Mackay DJG
Publication type: Article
Publication status: Published
Journal: European Journal of Human Genetics
Year: 2012
Volume: 20
Issue: 2
Pages: 240-243
Print publication date: 24/08/2011
ISSN (print): 1018-4813
ISSN (electronic): 1476-5438
Publisher: Nature Publishing Group
URL: http://dx.doi.org/10.1038/ejhg.2011.166
DOI: 10.1038/ejhg.2011.166
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