Genetic abnormalities in a large cohort of Coffin-Siris syndrome patients

Sekiguchi F 1 , Tsurusaki Y 1 , Okamoto N 2 , Teik KW 3 , Mizuno S 4 , Suzumura H 5 Show all authors , Isidor B 6 , Ong WP 3 , Haniffa M 3 , White SM 7 , Matsuo M 8 , Saito K 8 , Phadke S 9 , Kosho T 10 , Yap P 11 , Goyal M 12 , Clarke LA 13 , Sachdev R 14 , McGillivray G 7 , Leventer RJ 15 , Patel C 16 , Yamagata T 17 , Osaka H 17 , Hisaeda Y 18 , Ohashi H 19 , Shimizu K 19 , Nagasaki K 20 , Hamada J 21 , Dateki S 22 , Sato T 23 , Chinen Y 24 , Awaya T 25 , Kato T 26 , Iwanaga K 26 , Kawai M 26 , Matsuoka T 27 , Shimoji Y 27 , Tan TY 7 , Kapoor S 28 , Gregersen N 11 , Rossi M 29 , Marie-Laure M 29 , McGregor L 30 , Oishi K 31 , Mehta L 31 , Gillies G 32 , Lockhart PJ 32 , Pope K 32 , Shukla A 33 , Girisha KM 33 , Abdel-Salam GMH 34 , Mowat D 35 , Coman D 36 , Kim OH 37 , Cordier MP 38 , Gibson K 39 , Milunsky J 40 , Liebelt J 41 , Cox H 42 , El Chehadeh S 43 , Toutain A 44 , Saida K 1 , Aoi H 1 , Minase G 1 , Tsuchida N 1 , Iwama K 1 , Uchiyama Y 1 , Suzuki T 1 , Hamanaka K 1 , Azuma Y 1 , Fujita A 1 , Imagawa E 1 , Koshimizu E 1 , Takata A 1 , Mitsuhashi S 1 , Miyatake S 1 , Mizuguchi T 1 , Miyake N 1 , Matsumoto N 45

Affiliations 

  • 1 Department of Human Genetics, Graduate school of medicine, Yokohama City University, Yokohama, Japan
  • 2 Department of Medical Genetics, Osaka Women's and Children's Hospital, Osaka, Japan
  • 3 Department of Genetics, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia
  • 4 Department of Clinical Genetics, Central Hospital, Aichi Developmental Disability Center, Kasugai, Japan
  • 5 Department of Pediatrics, Dokkyo Medical University, Tochigi, Japan
  • 6 CHU Nantes, Service de Genetique Medicale, Nantes, France
  • 7 Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Australia
  • 8 Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan
  • 9 Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
  • 10 Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan
  • 11 Genetic Health Service New Zealand, Auckland, New Zealand
  • 12 Rare Disease Clinic, J K Lone Hospital, SMS Medical College, Jaipur, Rajasthan, India
  • 13 British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada
  • 14 Centre for Clinical Genetics, Sydney Children's Hospital, Randwick, NSW, Australia
  • 15 Royal Children's Hospital Department of Neurology, Murdoch Children's Research Institute and University of Melbourne Department of Pediatrics, Parkville, 3052, Australia
  • 16 Genetic Health Queensland, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia
  • 17 Department of Pediatrics, Jichi Medical University, Tochigi, Japan
  • 18 Department of Neonatology, Japanese Red Cross Medical Center, Tokyo, Japan
  • 19 Division of Medical Genetics, Saitama Children's Medical Center, Saitama, Japan
  • 20 Department of Homeostatic Regulation and Development, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
  • 21 Department of Pediatrics, Ehime University Graduate School of Medicine, Ehime, Japan
  • 22 Department of Pediatrics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
  • 23 Asahikawa-Kosei General Hospital, Hokkaido, Japan
  • 24 Department of Child Health and Welfare, Graduate School of Medicine, University of the Ryukyus, Nishihara, Japan
  • 25 Department of Anatomy and Developmental Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
  • 26 Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
  • 27 Department of General Pediatrics, Okinawa Prefectural Nanbu Medical Center and Children's Medical Center, Okinawa, Japan
  • 28 Division of Genetics, Department of Pediatrics, Maulana Azad Medical College, New Delhi, India
  • 29 Hospices Civils de Lyon, Service de Génétique, Centre de Référence Anomalies du Développement, and INSERM U1028, CNRS UMR5292, CRNL, GENDEV Team, UCBL1, Bron, France
  • 30 South Australian Clinical Genetics Service, SA Pathology, Women's and Children's Hospital, Adelaide, Australia
  • 31 Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
  • 32 Bruce Lefroy Centre for Genetic Health Research, Murdoch Children's Research Institute, Victoria, Australia
  • 33 Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India
  • 34 Department of Clinical Genetics, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt
  • 35 Department of Medical Genetics, Sydney Children's Hospital, Sydney, NSW, Australia
  • 36 Department of Paediatrics, The Wesley Hospital, Brisbane, QLD, Australia
  • 37 Department of Radiology, Ajou University Hospital, Suwon, Korea
  • 38 Service de Genetique, Hospices Civils de Lyon, Bron, France
  • 39 Genetic Health Service New Zealand, Christchurch Hospital, Christchurch, New Zealand
  • 40 Center for Human Genetics Inc, Cambridge, MA, USA
  • 41 South Australian Clinical Genetics Services, Women's and Children's Hospital, North Adelaide, Australia
  • 42 West Midlands Regional Genetics Service, Birmingham Women's NHS Foundation Trust, Birmingham Women's Hospital, Edgbaston, Birmingham, B15 2TG, UK
  • 43 Service de Genetique Medicale, Hopital de Hautepierre, Strasbourg, France
  • 44 Service de Genetique, CHRU de Tours, Tours, France
  • 45 Department of Human Genetics, Graduate school of medicine, Yokohama City University, Yokohama, Japan. naomat@yokohama-cu.ac.jp
J Hum Genet, 2019 Dec;64(12):1173-1186.
PMID: 31530938 DOI: 10.1038/s10038-019-0667-4

Abstract

Coffin-Siris syndrome (CSS, MIM#135900) is a congenital disorder characterized by coarse facial features, intellectual disability, and hypoplasia of the fifth digit and nails. Pathogenic variants for CSS have been found in genes encoding proteins in the BAF (BRG1-associated factor) chromatin-remodeling complex. To date, more than 150 CSS patients with pathogenic variants in nine BAF-related genes have been reported. We previously reported 71 patients of whom 39 had pathogenic variants. Since then, we have recruited an additional 182 CSS-suspected patients. We performed comprehensive genetic analysis on these 182 patients and on the previously unresolved 32 patients, targeting pathogenic single nucleotide variants, short insertions/deletions and copy number variations (CNVs). We confirmed 78 pathogenic variations in 78 patients. Pathogenic variations in ARID1B, SMARCB1, SMARCA4, ARID1A, SOX11, SMARCE1, and PHF6 were identified in 48, 8, 7, 6, 4, 1, and 1 patients, respectively. In addition, we found three CNVs including SMARCA2. Of particular note, we found a partial deletion of SMARCB1 in one CSS patient and we thoroughly investigated the resulting abnormal transcripts.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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