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


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.
1 Department of Genetics, United Laboratories, Tartu University Hospital , Tartu, Estonia .|2 Department of Pediatrics, University of Tartu , Tartu, Estonia .|3 Children's Clinic, Tartu University Hospital , Tartu, Estonia .
Mari-Anne
MA
Vals
1 Department of Genetics, United Laboratories, Tartu University Hospital , Tartu, Estonia .|2 Department of Pediatrics, University of Tartu , Tartu, Estonia .
Maria
M
Yakoreva
1 Department of Genetics, United Laboratories, Tartu University Hospital , Tartu, Estonia .|2 Department of Pediatrics, University of Tartu , Tartu, Estonia .
Tiina
T
Kahre
4 United Laboratories, Tartu University Hospital , Tartu, Estonia .
Pille
P
Mee
1 Department of Genetics, United Laboratories, Tartu University Hospital , Tartu, Estonia .|2 Department of Pediatrics, University of Tartu , Tartu, Estonia .
Kai
K
Muru
1 Department of Genetics, United Laboratories, Tartu University Hospital , Tartu, Estonia .
Kairit
K
Joost
1 Department of Genetics, United Laboratories, Tartu University Hospital , Tartu, Estonia .|2 Department of Pediatrics, University of Tartu , Tartu, Estonia .
Rita
R
Teek
5 Institute of Human Genetics , RWTH Aachen, Aachen, Germany .
Lukas
L
Soellner
5 Institute of Human Genetics , RWTH Aachen, Aachen, Germany .
Thomas
T
Eggermann
1 Department of Genetics, United Laboratories, Tartu University Hospital , Tartu, Estonia .|2 Department of Pediatrics, University of Tartu , Tartu, Estonia .
Katrin
K
Õunap
D001506:Beckwith-Wiedemann Syndrome / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D004957:Estonia; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D017527:Receptor, IGF Type 2 / Q000235:genetics / Q000378:metabolism; D056730:Silver-Russell Syndrome / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
D018797:Cell Cycle Proteins; C106464:PLAGL1 protein, human; D017527:Receptor, IGF Type 2; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins