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  • Oral presentation
  • Open Access

Genetic diagnosis of Beckwith Wiedemann syndrome and Silver-Russell syndrome

  • 2,
  • 1,
  • 1, 2,
  • 1,
  • 1,
  • 1 and
  • 1, 2
International Journal of Pediatric Endocrinology20132013 (Suppl 1) :O44

https://doi.org/10.1186/1687-9856-2013-S1-O44

  • Published:

Keywords

  • Microsatellite Marker
  • Chromosome 11p15
  • Genetic Diagnosis
  • Postnatal Growth
  • Large Patient Cohort

Beckwith-Wiedemann syndrome (BWS) is fetal overgrowth syndrome, whereas Silver-Russell syndrome (SRS) is characterized by pre- or postnatal growth retardation. BWS and SRS share molecular epigenetic defects in chromosome 11p15, where two imprinting centers, LIT1-differentially methylated region (MDR) and H19-DMR, exist. A small number of patients with SRS harbor maternal uniparental disomy of chromosome 7q as well. Extensive genetic analyses including methylation specific (MS) PCR-RFLP, MS-MLPA, microsatellite markers or MS-pyrosequencing analysis were performed using genomic DNA obtained from peripheral leukocytes to identify the epigenetic detects in patients with BWS and SRS. Ten out of 14 BWS patients (71.4%) showed hypomethylation in LIT1-DMR. One BWS patient harbored hypermethylation in H19-DMR (7.1%). Two BWS patients had both H19-DMR and LIT1-DMR defects, one of whom has paternal UPD at chr. 11 (14.3%). Eleven out of 13 SRS patients (78.6 %) showed hypomethylation in H19-DMR. One SRS patient (6.7%) had UPD at 7q. With MS-pyrosequencing analysis, epigenetic defects were identified in 93.1% of BWS patients and 85.7% of SRS patients. These positive rates are higher than previously reported positive rates, 80% in BWS and 50% in SRS. In addition, with MS-pyrosequencing analyses, quantification of methylation defects was available, which could identify partial methylation defects that were not revealed by MS-PCR-RFLP or MS-MLPA. The validity of MS-pyrosequencing method for the genetic diagnosis of BWS or SRS is needed to be investigated in a large patient cohort.

Authors’ Affiliations

(1)
Medical Genetics Center, University of Ulsan College of Medicine, Seoul, Korea
(2)
Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

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