Background:
The molecular etiology of Beckwith-Wiedemann syndrome (BWS) is complex and heterogeneous. Several subtypes of epigenetic-genetic alterations including aberrant methylation patterns, segmental uniparental disomy, single gene mutations, and copy number changes have been described. An integrated molecular approach to analyze the epigenetic-genetic alterations is required for accurate diagnosis of BWS.
Case presentation:
We reported two Chinese cases with BWS detected by genome-wide copy number analysis and locus-specific methylation profiling. Prenatal analysis on cord blood of patient 1 showed a de novo paternal origin duplication spanning 896Kb at 11p15.5. Patient 2 was referred at 2-month old and the genetic analysis showed a de novo 228.8Kb deletion at 11p15.5 telomeric end and a de novo duplication of 2.5 Mb at 11p15.5-15.4. Both the duplications are of paternal origin with gain of methylation at the imprinting center 1 and thus belong to the subgroup of a low tumor risk.
Conclusion:
Results from these two cases and other reported cases from literature indicated that paternally derived duplications at 11p15.5 region cause BWS. Combined chromosome microarray analysis and methylation profiling provided reliable diagnosis for this subtype of BWS. Characterization of genetic defects in BWS patients could lead to better understanding the genetic mechanisms of this clinically and genetically heterogeneous disorder.