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Article: Rare SUZ12 variants commonly cause an overgrowth phenotype

TitleRare SUZ12 variants commonly cause an overgrowth phenotype
Authors
KeywordsCohen‐Gibson syndrome
Polycomb repressive complex 2
SUZ12
SUZ12‐related overgrowth
Weaver syndrome
Issue Date2019
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.interscience.wiley.com/jpages/0148-7299:2/
Citation
American Journal of Medical Genetics Part C: Seminars in Medical Genetics, 2019, v. 181 n. 4, p. 532-547 How to Cite?
AbstractThe Polycomb repressive complex 2 is an epigenetic writer and recruiter with a role in transcriptional silencing. Constitutional pathogenic variants in its component proteins have been found to cause two established overgrowth syndromes: Weaver syndrome (EZH2‐related overgrowth) and Cohen‐Gibson syndrome (EED‐related overgrowth). Imagawa et al. (2017) initially reported a singleton female with a Weaver‐like phenotype with a rare coding SUZ12 variant—the same group subsequently reported two additional affected patients. Here we describe a further 10 patients (from nine families) with rare heterozygous SUZ12 variants who present with a Weaver‐like phenotype. We report four frameshift, two missense, one nonsense, and two splice site variants. The affected patients demonstrate variable pre‐ and postnatal overgrowth, dysmorphic features, musculoskeletal abnormalities and developmental delay/intellectual disability. Some patients have genitourinary and structural brain abnormalities, and there may be an association with respiratory issues. The addition of these 10 patients makes a compelling argument that rare pathogenic SUZ12 variants frequently cause overgrowth, physical abnormalities, and abnormal neurodevelopmental outcomes in the heterozygous state. Pathogenic SUZ12 variants may be de novo or inherited, and are sometimes inherited from a mildly‐affected parent. Larger samples sizes will be needed to elucidate whether one or more clinically‐recognizable syndromes emerge from different variant subtypes.
Persistent Identifierhttp://hdl.handle.net/10722/281233
ISSN
2019 Impact Factor: 7.101
2015 SCImago Journal Rankings: 2.315
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorCyrus, SS-
dc.contributor.authorCohen, ASA-
dc.contributor.authorAgbahovbe, R-
dc.contributor.authorAvela, K-
dc.contributor.authorYeung, KS-
dc.contributor.authorChung, BHY-
dc.contributor.authorLuk, HM-
dc.contributor.authorTkachenko, N-
dc.contributor.authorChoufani, S-
dc.contributor.authorWeksberg, R-
dc.contributor.authorLopez-Rangel, E-
dc.contributor.authorBrown, K-
dc.contributor.authorSanenz, MS-
dc.contributor.authorSvihovec, S-
dc.contributor.authorMcCandless, SE-
dc.contributor.authorBird, LM-
dc.contributor.authorGarcia, AG-
dc.contributor.authorCambello, MJ-
dc.contributor.authorMcWalter, K-
dc.contributor.authorSchnur, RE-
dc.contributor.authorAn, J-
dc.contributor.authorJones, SJM-
dc.contributor.authorBhalla, SK-
dc.contributor.authorPinz, H-
dc.contributor.authorBraddock, SR-
dc.contributor.authorGibson, WT-
dc.date.accessioned2020-03-09T09:51:55Z-
dc.date.available2020-03-09T09:51:55Z-
dc.date.issued2019-
dc.identifier.citationAmerican Journal of Medical Genetics Part C: Seminars in Medical Genetics, 2019, v. 181 n. 4, p. 532-547-
dc.identifier.issn1552-4868-
dc.identifier.urihttp://hdl.handle.net/10722/281233-
dc.description.abstractThe Polycomb repressive complex 2 is an epigenetic writer and recruiter with a role in transcriptional silencing. Constitutional pathogenic variants in its component proteins have been found to cause two established overgrowth syndromes: Weaver syndrome (EZH2‐related overgrowth) and Cohen‐Gibson syndrome (EED‐related overgrowth). Imagawa et al. (2017) initially reported a singleton female with a Weaver‐like phenotype with a rare coding SUZ12 variant—the same group subsequently reported two additional affected patients. Here we describe a further 10 patients (from nine families) with rare heterozygous SUZ12 variants who present with a Weaver‐like phenotype. We report four frameshift, two missense, one nonsense, and two splice site variants. The affected patients demonstrate variable pre‐ and postnatal overgrowth, dysmorphic features, musculoskeletal abnormalities and developmental delay/intellectual disability. Some patients have genitourinary and structural brain abnormalities, and there may be an association with respiratory issues. The addition of these 10 patients makes a compelling argument that rare pathogenic SUZ12 variants frequently cause overgrowth, physical abnormalities, and abnormal neurodevelopmental outcomes in the heterozygous state. Pathogenic SUZ12 variants may be de novo or inherited, and are sometimes inherited from a mildly‐affected parent. Larger samples sizes will be needed to elucidate whether one or more clinically‐recognizable syndromes emerge from different variant subtypes.-
dc.languageeng-
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.interscience.wiley.com/jpages/0148-7299:2/-
dc.relation.ispartofAmerican Journal of Medical Genetics Part C: Seminars in Medical Genetics-
dc.rightsPreprint This is the pre-peer reviewed version of the following article: [FULL CITE], which has been published in final form at [Link to final article using the DOI]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. Postprint This is the peer reviewed version of the following article: [FULL CITE], which has been published in final form at [Link to final article using the DOI]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.-
dc.subjectCohen‐Gibson syndrome-
dc.subjectPolycomb repressive complex 2-
dc.subjectSUZ12-
dc.subjectSUZ12‐related overgrowth-
dc.subjectWeaver syndrome-
dc.titleRare SUZ12 variants commonly cause an overgrowth phenotype-
dc.typeArticle-
dc.identifier.emailYeung, KS: ksyyeung@hku.hk-
dc.identifier.emailChung, BHY: bhychung@hku.hk-
dc.identifier.emailLuk, HM: lukhm@hku.hk-
dc.identifier.authorityChung, BHY=rp00473-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/ajmg.c.31748-
dc.identifier.scopuseid_2-s2.0-85075391653-
dc.identifier.hkuros309271-
dc.identifier.volume181-
dc.identifier.issue4-
dc.identifier.spage532-
dc.identifier.epage547-
dc.identifier.isiWOS:000496752500001-
dc.publisher.placeUnited States-
dc.identifier.issnl1552-4868-

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