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Familial STAG2 germline mutation defines a new human cohesinopathy
We characterize a novel human cohesinopathy originated from a familial germline mutation of the gene encoding the cohesin subunit STAG2, which we propose to call STAG2-related X-linked Intellectual Deficiency. Five individuals carry a STAG2 p.Ser327Asn (c.980 G > A) variant that perfectly cosegre...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5677968/ https://www.ncbi.nlm.nih.gov/pubmed/29263825 http://dx.doi.org/10.1038/s41525-017-0009-4 |
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author | Soardi, Fernanda C. Machado-Silva, Alice Linhares, Natália D. Zheng, Ge Qu, Qianhui Pena, Heloísa B. Martins, Thaís M. M. Vieira, Helaine G. S. Pereira, Núbia B. Melo-Minardi, Raquel C. Gomes, Carolina C. Gomez, Ricardo S. Gomes, Dawidson A. Pires, Douglas E. V. Ascher, David B. Yu, Hongtao Pena, Sérgio D. J. |
author_facet | Soardi, Fernanda C. Machado-Silva, Alice Linhares, Natália D. Zheng, Ge Qu, Qianhui Pena, Heloísa B. Martins, Thaís M. M. Vieira, Helaine G. S. Pereira, Núbia B. Melo-Minardi, Raquel C. Gomes, Carolina C. Gomez, Ricardo S. Gomes, Dawidson A. Pires, Douglas E. V. Ascher, David B. Yu, Hongtao Pena, Sérgio D. J. |
author_sort | Soardi, Fernanda C. |
collection | PubMed |
description | We characterize a novel human cohesinopathy originated from a familial germline mutation of the gene encoding the cohesin subunit STAG2, which we propose to call STAG2-related X-linked Intellectual Deficiency. Five individuals carry a STAG2 p.Ser327Asn (c.980 G > A) variant that perfectly cosegregates with a phenotype of syndromic mental retardation in a characteristic X-linked recessive pattern. Although patient-derived cells did not show overt sister-chromatid cohesion defects, they exhibited altered cell cycle profiles and gene expression patterns that were consistent with cohesin deficiency. The protein level of STAG2 in patient cells was normal. Interestingly, STAG2 S327 is located at a conserved site crucial for binding to SCC1 and cohesin regulators. When expressed in human cells, the STAG2 p.Ser327Asn mutant is defective in binding to SCC1 and other cohesin subunits and regulators. Thus, decreased amount of intact cohesin likely underlies the phenotypes of STAG2-SXLID. Intriguingly, recombinant STAG2 p.Ser327Asn binds normally to SCC1, WAPL, and SGO1 in vitro, suggesting the existence of unknown in vivo mechanisms that regulate the interaction between STAG2 and SCC1. |
format | Online Article Text |
id | pubmed-5677968 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-56779682017-12-20 Familial STAG2 germline mutation defines a new human cohesinopathy Soardi, Fernanda C. Machado-Silva, Alice Linhares, Natália D. Zheng, Ge Qu, Qianhui Pena, Heloísa B. Martins, Thaís M. M. Vieira, Helaine G. S. Pereira, Núbia B. Melo-Minardi, Raquel C. Gomes, Carolina C. Gomez, Ricardo S. Gomes, Dawidson A. Pires, Douglas E. V. Ascher, David B. Yu, Hongtao Pena, Sérgio D. J. NPJ Genom Med Article We characterize a novel human cohesinopathy originated from a familial germline mutation of the gene encoding the cohesin subunit STAG2, which we propose to call STAG2-related X-linked Intellectual Deficiency. Five individuals carry a STAG2 p.Ser327Asn (c.980 G > A) variant that perfectly cosegregates with a phenotype of syndromic mental retardation in a characteristic X-linked recessive pattern. Although patient-derived cells did not show overt sister-chromatid cohesion defects, they exhibited altered cell cycle profiles and gene expression patterns that were consistent with cohesin deficiency. The protein level of STAG2 in patient cells was normal. Interestingly, STAG2 S327 is located at a conserved site crucial for binding to SCC1 and cohesin regulators. When expressed in human cells, the STAG2 p.Ser327Asn mutant is defective in binding to SCC1 and other cohesin subunits and regulators. Thus, decreased amount of intact cohesin likely underlies the phenotypes of STAG2-SXLID. Intriguingly, recombinant STAG2 p.Ser327Asn binds normally to SCC1, WAPL, and SGO1 in vitro, suggesting the existence of unknown in vivo mechanisms that regulate the interaction between STAG2 and SCC1. Nature Publishing Group UK 2017-03-20 /pmc/articles/PMC5677968/ /pubmed/29263825 http://dx.doi.org/10.1038/s41525-017-0009-4 Text en © The Author(s) 2017 This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Soardi, Fernanda C. Machado-Silva, Alice Linhares, Natália D. Zheng, Ge Qu, Qianhui Pena, Heloísa B. Martins, Thaís M. M. Vieira, Helaine G. S. Pereira, Núbia B. Melo-Minardi, Raquel C. Gomes, Carolina C. Gomez, Ricardo S. Gomes, Dawidson A. Pires, Douglas E. V. Ascher, David B. Yu, Hongtao Pena, Sérgio D. J. Familial STAG2 germline mutation defines a new human cohesinopathy |
title | Familial STAG2 germline mutation defines a new human cohesinopathy |
title_full | Familial STAG2 germline mutation defines a new human cohesinopathy |
title_fullStr | Familial STAG2 germline mutation defines a new human cohesinopathy |
title_full_unstemmed | Familial STAG2 germline mutation defines a new human cohesinopathy |
title_short | Familial STAG2 germline mutation defines a new human cohesinopathy |
title_sort | familial stag2 germline mutation defines a new human cohesinopathy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5677968/ https://www.ncbi.nlm.nih.gov/pubmed/29263825 http://dx.doi.org/10.1038/s41525-017-0009-4 |
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