Phenotypic spectrum and extent of DNA methylation defects associated with multilocus imprinting disturbances

Susanne Bens; Julia Kolarova; Jasmin Beygo; Karin Buiting; Almuth Caliebe; Thomas Eggermann; Gabriele Gillessen-Kaesbach; Dirk Prawitt; Susanne Thiele-Schmitz; Matthias Begemann; Thorsten Enklaar; Jana Gutwein; Andrea Haake; Ulrike Paul; Julia Richter; Lukas Soellner; Inga Vater; David Monk; Bernhard Horsthemke; Ole Ammerpohl; Reiner Siebert

doi:10.2217/epi-2016-0007

Phenotypic spectrum and extent of DNA methylation defects associated with multilocus imprinting disturbances

Susanne Bens, Julia Kolarova, Jasmin Beygo, Karin Buiting, Almuth Caliebe, Thomas Eggermann, Gabriele Gillessen-Kaesbach, Dirk Prawitt, Susanne Thiele-Schmitz, Matthias Begemann, Thorsten Enklaar, Jana Gutwein, Andrea Haake, Ulrike Paul, Julia Richter, Lukas Soellner, Inga Vater, David Monk, Bernhard Horsthemke, Ole AmmerpohlReiner Siebert

Abstract

AIM: To characterize the genotypic and phenotypic extent of multilocus imprinting disturbances (MLID).

MATERIALS & METHODS: We analyzed 37 patients with imprinting disorders (explorative cohort) for DNA methylation changes using the Infinium HumanMethylation450 BeadChip. For validation, three independent cohorts with imprinting disorders or cardinal features thereof were analyzed (84 patients with imprinting disorders, 52 with growth disorder, 81 with developmental delay).

RESULTS: In the explorative cohort 21 individuals showed array-based MLID with each one displaying an Angelman or Temple syndrome phenotype, respectively. Epimutations in ZDBF2 and FAM50B were associated with severe MLID regarding number of affected regions. By targeted analysis we identified methylation changes of ZDBF2 and FAM50B also in the three validation cohorts.

CONCLUSION: We corroborate epimutations in ZDBF2 and FAM50B as frequent changes in MLID whereas these rarely occur in other patients with cardinal features of imprinting disorders. Moreover, we show cell lineage specific differences in the genomic extent of FAM50B epimutation.

Original language	English
Journal	Epigenomics
Volume	8
Issue number	6
Pages (from-to)	801-16
Number of pages	16
ISSN	1750-1911
DOIs	https://doi.org/10.2217/epi-2016-0007
Publication status	Published - 06.2016

Research Areas and Centers

Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)

DFG Research Classification Scheme

2.22-17 Endocrinology, Diabetology, Metabolism
2.22-20 Pediatric and Adolescent Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Bens, S., Kolarova, J., Beygo, J., Buiting, K., Caliebe, A., Eggermann, T., Gillessen-Kaesbach, G., Prawitt, D., Thiele-Schmitz, S., Begemann, M., Enklaar, T., Gutwein, J., Haake, A., Paul, U., Richter, J., Soellner, L., Vater, I., Monk, D., Horsthemke, B., ... Siebert, R. (2016). Phenotypic spectrum and extent of DNA methylation defects associated with multilocus imprinting disturbances. Epigenomics, 8(6), 801-16. https://doi.org/10.2217/epi-2016-0007

@article{32579961c1124ab6917b8739d02da48b,

title = "Phenotypic spectrum and extent of DNA methylation defects associated with multilocus imprinting disturbances",

abstract = "AIM: To characterize the genotypic and phenotypic extent of multilocus imprinting disturbances (MLID).MATERIALS & METHODS: We analyzed 37 patients with imprinting disorders (explorative cohort) for DNA methylation changes using the Infinium HumanMethylation450 BeadChip. For validation, three independent cohorts with imprinting disorders or cardinal features thereof were analyzed (84 patients with imprinting disorders, 52 with growth disorder, 81 with developmental delay).RESULTS: In the explorative cohort 21 individuals showed array-based MLID with each one displaying an Angelman or Temple syndrome phenotype, respectively. Epimutations in ZDBF2 and FAM50B were associated with severe MLID regarding number of affected regions. By targeted analysis we identified methylation changes of ZDBF2 and FAM50B also in the three validation cohorts.CONCLUSION: We corroborate epimutations in ZDBF2 and FAM50B as frequent changes in MLID whereas these rarely occur in other patients with cardinal features of imprinting disorders. Moreover, we show cell lineage specific differences in the genomic extent of FAM50B epimutation.",

author = "Susanne Bens and Julia Kolarova and Jasmin Beygo and Karin Buiting and Almuth Caliebe and Thomas Eggermann and Gabriele Gillessen-Kaesbach and Dirk Prawitt and Susanne Thiele-Schmitz and Matthias Begemann and Thorsten Enklaar and Jana Gutwein and Andrea Haake and Ulrike Paul and Julia Richter and Lukas Soellner and Inga Vater and David Monk and Bernhard Horsthemke and Ole Ammerpohl and Reiner Siebert",

year = "2016",

month = jun,

doi = "10.2217/epi-2016-0007",

language = "English",

volume = "8",

pages = "801--16",

journal = "Epigenomics",

issn = "1750-1911",

number = "6",

}

Bens, S, Kolarova, J, Beygo, J, Buiting, K, Caliebe, A, Eggermann, T, Gillessen-Kaesbach, G, Prawitt, D, Thiele-Schmitz, S, Begemann, M, Enklaar, T, Gutwein, J, Haake, A, Paul, U, Richter, J, Soellner, L, Vater, I, Monk, D, Horsthemke, B, Ammerpohl, O & Siebert, R 2016, 'Phenotypic spectrum and extent of DNA methylation defects associated with multilocus imprinting disturbances', Epigenomics, vol. 8, no. 6, pp. 801-16. https://doi.org/10.2217/epi-2016-0007

TY - JOUR

T1 - Phenotypic spectrum and extent of DNA methylation defects associated with multilocus imprinting disturbances

AU - Bens, Susanne

AU - Kolarova, Julia

AU - Beygo, Jasmin

AU - Buiting, Karin

AU - Caliebe, Almuth

AU - Eggermann, Thomas

AU - Gillessen-Kaesbach, Gabriele

AU - Prawitt, Dirk

AU - Thiele-Schmitz, Susanne

AU - Begemann, Matthias

AU - Enklaar, Thorsten

AU - Gutwein, Jana

AU - Haake, Andrea

AU - Paul, Ulrike

AU - Richter, Julia

AU - Soellner, Lukas

AU - Vater, Inga

AU - Monk, David

AU - Horsthemke, Bernhard

AU - Ammerpohl, Ole

AU - Siebert, Reiner

PY - 2016/6

Y1 - 2016/6

N2 - AIM: To characterize the genotypic and phenotypic extent of multilocus imprinting disturbances (MLID).MATERIALS & METHODS: We analyzed 37 patients with imprinting disorders (explorative cohort) for DNA methylation changes using the Infinium HumanMethylation450 BeadChip. For validation, three independent cohorts with imprinting disorders or cardinal features thereof were analyzed (84 patients with imprinting disorders, 52 with growth disorder, 81 with developmental delay).RESULTS: In the explorative cohort 21 individuals showed array-based MLID with each one displaying an Angelman or Temple syndrome phenotype, respectively. Epimutations in ZDBF2 and FAM50B were associated with severe MLID regarding number of affected regions. By targeted analysis we identified methylation changes of ZDBF2 and FAM50B also in the three validation cohorts.CONCLUSION: We corroborate epimutations in ZDBF2 and FAM50B as frequent changes in MLID whereas these rarely occur in other patients with cardinal features of imprinting disorders. Moreover, we show cell lineage specific differences in the genomic extent of FAM50B epimutation.

AB - AIM: To characterize the genotypic and phenotypic extent of multilocus imprinting disturbances (MLID).MATERIALS & METHODS: We analyzed 37 patients with imprinting disorders (explorative cohort) for DNA methylation changes using the Infinium HumanMethylation450 BeadChip. For validation, three independent cohorts with imprinting disorders or cardinal features thereof were analyzed (84 patients with imprinting disorders, 52 with growth disorder, 81 with developmental delay).RESULTS: In the explorative cohort 21 individuals showed array-based MLID with each one displaying an Angelman or Temple syndrome phenotype, respectively. Epimutations in ZDBF2 and FAM50B were associated with severe MLID regarding number of affected regions. By targeted analysis we identified methylation changes of ZDBF2 and FAM50B also in the three validation cohorts.CONCLUSION: We corroborate epimutations in ZDBF2 and FAM50B as frequent changes in MLID whereas these rarely occur in other patients with cardinal features of imprinting disorders. Moreover, we show cell lineage specific differences in the genomic extent of FAM50B epimutation.

U2 - 10.2217/epi-2016-0007

DO - 10.2217/epi-2016-0007

M3 - Journal articles

C2 - 27323310

SN - 1750-1911

VL - 8

SP - 801

EP - 816

JO - Epigenomics

JF - Epigenomics

IS - 6

ER -

Phenotypic spectrum and extent of DNA methylation defects associated with multilocus imprinting disturbances

Abstract

Research Areas and Centers

DFG Research Classification Scheme

UN SDGs

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