TY - JOUR
T1 - Genome-wide methylation profiling of Beckwith-Wiedemann syndrome patients without molecular confirmation after routine diagnostics
AU - Krzyzewska, I. M.
AU - Alders, M.
AU - Maas, S. M.
AU - Bliek, J.
AU - Venema, A.
AU - Henneman, P.
AU - Rezwan, F. I.
AU - Lip, K. V. D.
AU - Mul, A. N.
AU - Mackay, D. J. G.
AU - Mannens, M. M. A. M.
PY - 2019/3/21
Y1 - 2019/3/21
N2 - Beckwith-Wiedemann syndrome (BWS) is caused due to the disturbance of imprinted genes at chromosome 11p15. The molecular confirmation of this syndrome is possible in approximately 85% of the cases, whereas in the remaining 15% of the cases, the underlying defect remains unclear. The goal of our research was to identify new epigenetic loci related to BWS. We studied a group of 25 patients clinically diagnosed with BWS but without molecular conformation after DNA diagnostics and performed a whole genome methylation analysis using the HumanMethylation450 Array (Illumina). We found hypermethylation throughout the methylome in two BWS patients. The hypermethylated sites in these patients overlapped and included both non-imprinted and imprinted regions. This finding was not previously described in any BWS-diagnosed patient. Furthermore, one BWS patient exhibited aberrant methylation in four maternally methylated regions - IGF1R, NHP2L1, L3MBTL, and ZDBF2 - that overlapped with the differentially methylated regions found in BWS patients with multi-locus imprinting disturbance (MLID). This finding suggests that the BWS phenotype can result from MLID without detectable methylation defects in the primarily disease-associated loci (11p15). Another patient manifested small but significant aberrant methylation in disease-associated loci at 11p near H19, possibly confirming the diagnosis in this patient.
AB - Beckwith-Wiedemann syndrome (BWS) is caused due to the disturbance of imprinted genes at chromosome 11p15. The molecular confirmation of this syndrome is possible in approximately 85% of the cases, whereas in the remaining 15% of the cases, the underlying defect remains unclear. The goal of our research was to identify new epigenetic loci related to BWS. We studied a group of 25 patients clinically diagnosed with BWS but without molecular conformation after DNA diagnostics and performed a whole genome methylation analysis using the HumanMethylation450 Array (Illumina). We found hypermethylation throughout the methylome in two BWS patients. The hypermethylated sites in these patients overlapped and included both non-imprinted and imprinted regions. This finding was not previously described in any BWS-diagnosed patient. Furthermore, one BWS patient exhibited aberrant methylation in four maternally methylated regions - IGF1R, NHP2L1, L3MBTL, and ZDBF2 - that overlapped with the differentially methylated regions found in BWS patients with multi-locus imprinting disturbance (MLID). This finding suggests that the BWS phenotype can result from MLID without detectable methylation defects in the primarily disease-associated loci (11p15). Another patient manifested small but significant aberrant methylation in disease-associated loci at 11p near H19, possibly confirming the diagnosis in this patient.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85063346429&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30898153
U2 - https://doi.org/10.1186/s13148-019-0649-6
DO - https://doi.org/10.1186/s13148-019-0649-6
M3 - Article
C2 - 30898153
SN - 1868-7075
VL - 11
JO - Clinical epigenetics
JF - Clinical epigenetics
IS - 1
M1 - 53
ER -