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Clinical Trial
. 2015 Dec;19(12):684-91.
doi: 10.1089/gtmb.2015.0163. Epub 2015 Oct 27.

The Frequency of Methylation Abnormalities Among Estonian Patients Selected by Clinical Diagnostic Scoring Systems for Silver-Russell Syndrome and Beckwith-Wiedemann Syndrome

Mari-Anne Vals  1   2   3 , Maria Yakoreva  1   2 , Tiina Kahre  1   2 , Pille Mee  4 , Kai Muru  1   2 , Kairit Joost  1 , Rita Teek  1   2 , Lukas Soellner  5 , Thomas Eggermann  5 , Katrin Õunap  1   2
Affiliations
Clinical Trial

The Frequency of Methylation Abnormalities Among Estonian Patients Selected by Clinical Diagnostic Scoring Systems for Silver-Russell Syndrome and Beckwith-Wiedemann Syndrome

Mari-Anne Vals et al. Genet Test Mol Biomarkers. 2015 Dec.

Abstract

Aims: To study the frequency of methylation abnormalities among Estonian patients selected according to published clinical diagnostic scoring systems for Silver-Russell syndrome (SRS) and Beckwith-Wiedemann syndrome (BWS).

Materials and methods: Forty-eight patients with clinical suspicion of SRS (n = 20) or BWS (n = 28) were included in the study group, to whom methylation-specific multiplex ligation-dependant probe amplification analysis of 11p15 region was made. In addition, to patients with minimal diagnostic score for either SRS or BWS, multilocus methylation-specific single nucleotide primer extension assay was performed.

Results: Five (38%) SRS patients with positive clinical scoring had abnormal methylation pattern at chromosome 11p15, whereas in the BWS group, only one patient was diagnosed with imprinting control region 2 (ICR2) hypomethylation (8%). An unexpected hypomethylation of the PLAGL1 (6q24) and IGF2R (6q25) genes in the patient with the highest BWS scoring was found.

Conclusions: Compared to BWS, diagnostic criteria used for selecting SRS patients gave us a similar detection rate of 11p15 imprinting disorders as seen in other studies. A more careful selection of patients with possible BWS should be considered to improve the detection of molecularly confirmed cases. Genome-wide multilocus methylation tests could be used in routine clinical practice as it increases the detection rates of imprinting disorders.

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Figures

<b>FIG. 1.</b>
FIG. 1.
(a) Patient 1 in the Beckwith–Wiedemann syndrome (BWS) group as a newborn and (b) at the age of 3 years. Note the characteristic BWS facies.
See this image and copyright information in PMC

References

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    1. Baskin B, et al. (2014) High frequency of copy number variations (CNVs) in the chromosome 11p15 region in patients with Beckwith-Wiedemann syndrome. Hum Genet 133:321–330 - PubMed
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    1. Bliek J, et al. (2009) Hypomethylation at multiple maternally methylated imprinted regions including PLAGL1 and GNAS loci in Beckwith-Wiedemann syndrome. Eur J Human Genet 17:611–619 - PMC - PubMed
    1. Boonen SE, et al. (2013) Transient neonatal diabetes, ZFP57, and hypomethylation of multiple imprinted loci: a detailed follow-up. Diabetes Care 36:505–512 - PMC - PubMed

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