| Author | Soardi, Fernanda Caroline | |
| Author | Silva, Alice Machado | |
| Author | Linhares, Natália D. | |
| Author | Zheng, Ge | |
| Author | Qu, Qianhui | |
| Author | Pena, Heloísa Barbosa | |
| Author | Martins, Thaís Maria da Mata | |
| Author | Vieira, Helaine Graziele Santos | |
| Author | Pereira, Núbia Barbosa | |
| Author | Minardi, Raquel Cardoso de Melo | |
| Author | Gomes, Carolina Cavalieri | |
| Author | Gomez, Ricardo S. | |
| Author | Gomes, Dawidson Assis | |
| Author | Pires, Douglas Eduardo Valente | |
| Author | Ascher, David Benjamin | |
| Author | Pena, Sérgio Danilo Junho | |
| Access date | 2018-03-13T13:15:54Z | |
| Available date | 2018-03-13T13:15:54Z | |
| Document date | 2017 | |
| Citation | SOARDI, Fernanda Caroline et al. Familial STAG2 germline mutation defines a new human cohesinopathy. NPJ Genom Med., v. 2, n.1, art. 7, 2017 | pt_BR |
| ISSN | 2056-7944 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/25272 | |
| Language | eng | pt_BR |
| Publisher | Nature Publishing Group | pt_BR |
| Rights | restricted access | pt_BR |
| Subject in Portuguese | STAG2 gene | pt_BR |
| Title | Familial STAG2 germline mutation defines a new human cohesinopathy. | pt_BR |
| Type | Article | |
| Abstract | 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. | pt_BR |
| Affilliation | GENE—Núcleo de Genética Médica, Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Faculdade de Medicina. Laboratório de Genômica Clínica. Belo Horizonte, MG, Brazil | pt_BR |
| Affilliation | GENE—Núcleo de Genética Médica, Belo Horizonte, MG, Brazil | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Faculdade de Medicina. Laboratório de Genômica Clínica. Belo Horizonte, MG, Brazil | pt_BR |
| Affilliation | University of Texas Southwestern Medical Center. Howard Hughes Medical Institute. Department of Pharmacology. Dallas, TX, USA | pt_BR |
| Affilliation | University of Texas Southwestern Medical Center. Howard Hughes Medical Institute. Department of Pharmacology. Dallas, TX, USA | pt_BR |
| Affilliation | GENE—Núcleo de Genética Médica, Belo Horizonte, MG, Brazil | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil | pt_BR |
| Affilliation | Universidade Federal de Minas. Instituto de Ciências Biológicas. Departamento de Patologia Geral. Belo Horizonte, MG, Brazil | pt_BR |
| Affilliation | Universidade Federal de Minas. Instituto de Ciências Exatas. Departamento de Ciência da Computação. Belo Horizonte, MG, Brazil | pt_BR |
| Affilliation | Universidade Federal de Minas. Instituto de Ciências Biológicas. Departamento de Patologia Geral. Belo Horizonte, MG, Brazil | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Faculdade de Odontologia. Departamento de Clínica. Patologia e Cirurgia Odontológicas. Belo Horizonte, MG, Brazil | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil/University of Cambridge. Department of Biochemistry. Cambridge, UK/University of Melbourne. Department of Biochemistry. Victoria, Australia | pt_BR |
| Affilliation | University of Texas Southwestern Medical Center. Howard Hughes Medical Institute. Department of Pharmacology. Dallas, TX, USA | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Faculdade de Medicina. Laboratório de Genômica Clínica. Belo Horizonte, MG, Brazil | pt_BR |
| Subject | STAG2 gene | pt_BR |
| Subject | X-linked inheritance | pt_BR |
| Subject | SGO1 gene | pt_BR |
| Subject | Germ-Line Mutation | pt_BR |
| Subject | Chromatids | pt_BR |
| Subject | Mental Retardation | pt_BR |
| e-ISSN | 10.1038/s41525-017-0009-4 | |
| Embargo date | 2024-01-01 | |
