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Genome-wide methylation profiling of Beckwith Wiedemann syndrome patients without molecular confirmation after routine diagnostics

Genome-wide methylation profiling of Beckwith Wiedemann syndrome patients without molecular confirmation after routine diagnostics
Genome-wide methylation profiling of Beckwith Wiedemann syndrome patients without molecular confirmation after routine diagnostics
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.
1868-7075
53
Krzyzewska, I.M.
f7ec5e5a-6b30-4dcf-aa07-a59bf490c75c
Alders, M.
346d662f-e908-4f6e-8de8-b37ee8868f2e
Maas, S.M.
4111831e-2fc9-485f-892f-b07e575867f0
Bliek, J.
70763bb6-0210-4e57-ac42-d4a91ea60155
Venema, A.
1d3fd37b-26a1-430a-9e72-6b9570e3023b
Henneman, P.
4700050b-429e-4087-9b5d-4e188e56e37f
Rezwan, Faisal I
203f8f38-1f5d-485b-ab11-c546b4276338
Lip, K.V.D.
1fbe694d-f802-44c3-963f-4bd7e2c65fff
Mul, A.N.
10689627-22c6-42ff-a927-ebf5f6efb0ec
Mackay, Deborah
588a653e-9785-4a00-be71-4e547850ee4a
Mannens, Marcel M.A.M.
bb288561-4e69-4243-956b-894269170cd1
Krzyzewska, I.M.
f7ec5e5a-6b30-4dcf-aa07-a59bf490c75c
Alders, M.
346d662f-e908-4f6e-8de8-b37ee8868f2e
Maas, S.M.
4111831e-2fc9-485f-892f-b07e575867f0
Bliek, J.
70763bb6-0210-4e57-ac42-d4a91ea60155
Venema, A.
1d3fd37b-26a1-430a-9e72-6b9570e3023b
Henneman, P.
4700050b-429e-4087-9b5d-4e188e56e37f
Rezwan, Faisal I
203f8f38-1f5d-485b-ab11-c546b4276338
Lip, K.V.D.
1fbe694d-f802-44c3-963f-4bd7e2c65fff
Mul, A.N.
10689627-22c6-42ff-a927-ebf5f6efb0ec
Mackay, Deborah
588a653e-9785-4a00-be71-4e547850ee4a
Mannens, Marcel M.A.M.
bb288561-4e69-4243-956b-894269170cd1

Krzyzewska, I.M., Alders, M., Maas, S.M., Bliek, J., Venema, A., Henneman, P., Rezwan, Faisal I, Lip, K.V.D., Mul, A.N., Mackay, Deborah and Mannens, Marcel M.A.M. (2019) Genome-wide methylation profiling of Beckwith Wiedemann syndrome patients without molecular confirmation after routine diagnostics. Clinical Epigenetics, 11 (1), 53. (doi:10.1186/s13148-019-0649-6).

Record type: Article

Abstract

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.

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Accepted/In Press date: 6 March 2019
Published date: 21 March 2019

Identifiers

Local EPrints ID: 429640
URI: https://eprints.soton.ac.uk/id/eprint/429640
ISSN: 1868-7075
PURE UUID: 67226995-530e-4d58-a901-93ef6d2bb56e
ORCID for Faisal I Rezwan: ORCID iD orcid.org/0000-0001-9921-222X
ORCID for Deborah Mackay: ORCID iD orcid.org/0000-0003-3088-4401

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Date deposited: 02 Apr 2019 16:30
Last modified: 19 Jul 2019 01:06

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Contributors

Author: I.M. Krzyzewska
Author: M. Alders
Author: S.M. Maas
Author: J. Bliek
Author: A. Venema
Author: P. Henneman
Author: Faisal I Rezwan ORCID iD
Author: K.V.D. Lip
Author: A.N. Mul
Author: Deborah Mackay ORCID iD
Author: Marcel M.A.M. Mannens

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