Journal article
Familial stag2 germline mutation defines a new human cohesinopathy
FC Soardi, A Machado-Silva, ND Linhares, G Zheng, Q Qu, HB Pena, TMM Martins, HGS Vieira, NB Pereira, RC Melo-Minardi, CC Gomes, RS Gomez, DA Gomes, DEV Pires, DB Ascher, H Yu, SDJ Pena
Npj Genomic Medicine | NATURE PUBLISHING GROUP | Published : 2017
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..
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Awarded by Howard Hughes Medical Institute
Funding Acknowledgements
We are grateful to the patients and their family. Their cooperation made this work possible. F.C.S. was initially supported by a visiting researcher program fellowship from Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG) (BPV-00059-14) and by a fellowship from the Programa de Formacao de Recursos Humanos em Areas Estrategicas (RHAE) of the Conselho Nacional de Pesquisa (CNPq) (351030/2015-8). A.M.-S. was also supported by a fellowship from the Programa de Formacao de Recursos Humanos em Areas Estrategicas (RHAE) of the Conselho Nacional de Pesquisa (CNPq). N.D.L. was supported by a fellowship from Programa Nacional de Pos-doutorado (PNPD) Institucional of Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) (2792/2011). D.B.A. and D.E.V.P. received funding from a Newton Fund RCUK-CONFAP Grant awarded by The Medical Research Council (MRC) and Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG) (MR/M026302/1). D.E.V.P. received support from the Rene Rachou Research Center (CPqRR/FIOCRUZ Minas), Brazil. D.B.A. was supported by an NHMRC CJ Martin Fellowship (APP1072476) and the Jack Brockhoff Foundation (JBF 4186, 2016). H.Y. is an Investigator with the Howard Hughes Medical Institute, and is supported by grants from the Cancer Prevention Research Institute of Texas (RP110465-P3 and RP120717-P2) and the Welch Foundation (I-1441). S.D.J.P. receives support as a Scientist 1A of the Conselho Nacional de Pesquisa (CNPq). The work done in Brazil was funded by the Conselho Nacional de Pesquisa (CNPq) and the Fundacao de Pesquisa do Estado de Minas Gerais (FAPEMIG).