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Review
. 2019 Dec;181(4):519-531.
doi: 10.1002/ajmg.c.31754. Epub 2019 Nov 14.

PRC2-complex related dysfunction in overgrowth syndromes: A review of EZH2, EED, and SUZ12 and their syndromic phenotypes

Sharri Cyrus  1 , Deepika Burkardt  2 , David D Weaver  3 , William T Gibson  1   4
Affiliations
Review

PRC2-complex related dysfunction in overgrowth syndromes: A review of EZH2, EED, and SUZ12 and their syndromic phenotypes

Sharri Cyrus et al. Am J Med Genet C Semin Med Genet. 2019 Dec.

Abstract

The EZH2, EED, and SUZ12 genes encode proteins that comprise core components of the polycomb repressive complex 2 (PRC2), an epigenetic "writer" with H3K27 methyltransferase activity, catalyzing the addition of up to three methyl groups on histone 3 at lysine residue 27 (H3K27). Partial loss-of-function variants in genes encoding the EZH2 and EED subunits of the complex lead to overgrowth, macrocephaly, advanced bone age, variable intellectual disability, and distinctive facial features. EZH2-associated overgrowth, caused by constitutional heterozygous mutations within Enhancer of Zeste homologue 2 (EZH2), has a phenotypic spectrum ranging from tall stature without obvious intellectual disability or dysmorphic features to classical Weaver syndrome (OMIM #277590). EED-associated overgrowth (Cohen-Gibson syndrome; OMIM #617561) is caused by germline heterozygous mutations in Embryonic Ectoderm Development (EED), and manifests overgrowth and intellectual disability (OGID), along with other features similar to Weaver syndrome. Most recently, rare coding variants in SUZ12 have also been described that present with clinical characteristics similar to the previous two syndromes. Here we review the PRC2 complex and clinical syndromes of OGID associated with core components EZH2, EED, and SUZ12.

Keywords: Cohen-Gibson syndrome; SUZ12-related overgrowth; Weaver syndrome; overgrowth; polycomb repressive complex 2.

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References

REFERENCES

    1. Ai, S., Peng, Y., Li, C., Gu, F., Yu, X., Yue, Y., … He, A. (2017). EED orchestration of heart maturation through interaction with HDACs is H3K27me3-independent. eLife, 6, e24570. https://doi.org/10.7554/eLife.24570
    1. Alqarni, S. S. M., Murthy, A., Zhang, W., Przewloka, M. R., Silva, A. P. G., Watson, A. A., … Laue, E. D. (2014). Insight into the architecture of the NuRD complex: Structure of the RbAp48-MTA1 subcomplex. Journal of Biological Chemistry, 289(32), 21844-21855. https://doi.org/10.1074/jbc.M114.558940
    1. Beringer, M., Pisano, P., Di Carlo, V., Blanco, E., Chammas, P., Vizán, P., … Di Croce, L. (2016). EPOP functionally links Elongin and Polycomb in pluripotent stem cells. Molecular Cell, 64(4), 645-658. https://doi.org/10.1016/j.molcel.2016.10.018
    1. Beukelman, D. R., Hux, K., Dietz, A., McKelvey, M., & Weissling, K. (2015). Using visual scene displays as communication support options for people with chronic, severe aphasia: A summary of AAC research and future research directions. Augmentative and Alternative Communication, 31(3), 234-245. https://doi.org/10.3109/07434618.2015.1052152
    1. Birve, A., Sengupta, A. K., Beuchle, D., Larsson, J., Kennison, J. A., Rasmuson-Lestander, Å., & Müller, J. (2001). Su(z)12, a novel drosophila Polycomb group gene that is conserved in vertebrates and plants. Development, 128(17), 3371-3379.

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