STAG1 mutations cause a novel cohesinopathy characterised by unspecific syndromic intellectual disability.
Journal article

STAG1 mutations cause a novel cohesinopathy characterised by unspecific syndromic intellectual disability.

  • Lehalle D Fédération Hospitalo-Universitaire Médecine Translationnelle et Anomalies du Développement (TRANSLAD), Centre Hospitalier Universitaire Dijon, Dijon, France.
  • Mosca-Boidron AL Laboratoire de Cytogénétique, Centre Hospitalier Universitaire Dijon, Dijon, France.
  • Begtrup A GeneDx, 207 Perry Parkway, Gaithersburg, Maryland, USA.
  • Boute-Benejean O Service de génétique clinique, CHU Lille, Lille, France.
  • Charles P Genetic Department, University Hospital La Pitié Salpêtrière, Paris, France.
  • Cho MT GeneDx, 207 Perry Parkway, Gaithersburg, Maryland, USA.
  • Clarkson A Department of Clinical Genetics, Cambridge University Hospitals, Cambridge, UK.
  • Devinsky O Epilepsy Center, NYU Langone Medical Center, New York, New York, USA.
  • Duffourd Y Equipe GAD, EA4271, Faculté de Médecine, Université de Bourgogne Franche-Comté, Dijon, France.
  • Duplomb-Jego L Laboratoire de Cytogénétique, Centre Hospitalier Universitaire Dijon, Dijon, France.
  • Gérard B Laboratoire de biologie moléculaire, CHU Strasbourg, Strasbourg, France.
  • Jacquette A Genetic Department, University Hospital La Pitié Salpêtrière, Paris, France.
  • Kuentz P Laboratoire de Cytogénétique, Centre Hospitalier Universitaire Dijon, Dijon, France.
  • Masurel-Paulet A Fédération Hospitalo-Universitaire Médecine Translationnelle et Anomalies du Développement (TRANSLAD), Centre Hospitalier Universitaire Dijon, Dijon, France.
  • McDougall C Clinical Genetics Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
  • Moutton S Department of Clinical Genetics, Bordeaux, France.
  • Olivié H Department of Human Genetics and Centre for Developmental Disabilities, KU University Hospital Leuven, Leuven, Belgium.
  • Park SM Department of Clinical Genetics, Cambridge University Hospitals, Cambridge, UK.
  • Rauch A Institute of Medical Genetics, University of Zurich, Schwerzenbach-Zurich, Switzerland.
  • Revencu N Centre for Human Genetics, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium.
  • Rivière JB Fédération Hospitalo-Universitaire Médecine Translationnelle et Anomalies du Développement (TRANSLAD), Centre Hospitalier Universitaire Dijon, Dijon, France.
  • Rubin K University of Minnesota Children's Hospital, Minneapolis, Minnesota, USA.
  • Simonic I Department of Clinical Genetics, Cambridge University Hospitals, Cambridge, UK.
  • Shears DJ Oxford Centre for Genomic Medicine Nuffield Orthopaedic Centre, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 7HE.
  • Smol T Service de génétique clinique, CHU Lille, Lille, France.
  • Taylor Tavares AL Department of Clinical Genetics, Cambridge University Hospitals, Cambridge, UK.
  • Terhal P Department of Medical Genetics, University Medical Centre Utrecht, Utrecht, The Netherlands.
  • Thevenon J Fédération Hospitalo-Universitaire Médecine Translationnelle et Anomalies du Développement (TRANSLAD), Centre Hospitalier Universitaire Dijon, Dijon, France.
  • Van Gassen K Department of Medical Genetics, University Medical Centre Utrecht, Utrecht, The Netherlands.
  • Vincent-Delorme C Service de génétique clinique, CHU Lille, Lille, France.
  • Willemsen MH Department of Human Genetics, Radboud Institute for Molecular Life Sciences and Donders Centre for Neuroscience, Radboud University Medical Center, Nijmegen, The Netherlands.
  • Wilson GN Department of Pediatrics, Texas Tech University Health Science Center, Lubbock, Texas, USA.
  • Zackai E Department of Clinical Genetics, Bordeaux, France.
  • Zweier C Institute of Human Genetics, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Germany.
  • Callier P Fédération Hospitalo-Universitaire Médecine Translationnelle et Anomalies du Développement (TRANSLAD), Centre Hospitalier Universitaire Dijon, Dijon, France.
  • Thauvin-Robinet C Fédération Hospitalo-Universitaire Médecine Translationnelle et Anomalies du Développement (TRANSLAD), Centre Hospitalier Universitaire Dijon, Dijon, France.
  • Faivre L Fédération Hospitalo-Universitaire Médecine Translationnelle et Anomalies du Développement (TRANSLAD), Centre Hospitalier Universitaire Dijon, Dijon, France.
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  • 2017-01-26
Published in:
  • Journal of medical genetics. - 2017
English BACKGROUND
Cohesinopathies are rare neurodevelopmental disorders arising from a dysfunction in the cohesin pathway, which enables chromosome segregation and regulates gene transcription. So far, eight genes from this pathway have been reported in human disease. STAG1 belongs to the STAG subunit of the core cohesin complex, along with five other subunits. This work aimed to identify the phenotype ascribed to STAG1 mutations.


METHODS
Among patients referred for intellectual disability (ID) in genetics departments worldwide, array-comparative genomic hybridisation (CGH), gene panel, whole-exome sequencing or whole-genome sequencing were performed following the local diagnostic standards.


RESULTS
A mutation in STAG1 was identified in 17 individuals from 16 families, 9 males and 8 females aged 2-33 years. Four individuals harboured a small microdeletion encompassing STAG1; three individuals from two families had an intragenic STAG1 deletion. Six deletions were identified by array-CGH, one by whole-exome sequencing. Whole-exome sequencing found de novo heterozygous missense or frameshift STAG1 variants in eight patients, a panel of genes involved in ID identified a missense and a frameshift variant in two individuals. The 17 patients shared common facial features, with wide mouth and deep-set eyes. Four individuals had mild microcephaly, seven had epilepsy.


CONCLUSIONS
We report an international series of 17 individuals from 16 families presenting with syndromic unspecific ID that could be attributed to a STAG1 deletion or point mutation. This first series reporting the phenotype ascribed to mutation in STAG1 highlights the importance of data sharing in the field of rare disorders.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/134810
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