2. Academic Validation
  3. Mutations in STN1 cause Coats plus syndrome and are associated with genomic and telomere defects

Mutations in STN1 cause Coats plus syndrome and are associated with genomic and telomere defects

  • J Exp Med. 2016 Jul 25;213(8):1429-40. doi: 10.1084/jem.20151618.
Amos J Simon 1,  Atar Lev 2,  Yong Zhang 3,  Batia Weiss 4,  Anna Rylova 5,  Eran Eyal 6,  Nitzan Kol 6,  Ortal Barel 6,  Keren Cesarkas 6,  Michalle Soudack 7,  Noa Greenberg-Kushnir 3,  Michele Rhodes 3,  David L Wiest 3,  Ginette Schiby 8,  Iris Barshack 9,  Shulamit Katz 5,  Elon Pras 10,  Hana Poran 10,  Haike Reznik-Wolf 10,  Elena Ribakovsky 11,  Carlos Simon 12,  Wadi Hazou 13,  Yechezkel Sidi 13,  Avishay Lahad 14,  Hagar Katzir 15,  Shira Sagie 15,  Haifa A Aqeilan 16,  Galina Glousker 16,  Ninette Amariglio 17,  Yehuda Tzfati 16,  Sara Selig 18,  Gideon Rechavi 6,  Raz Somech 19
Affiliations

Affiliations

  • 1 Pediatric Department A and Immunology Service, Jeffrey Modell Foundation Center, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel Division of Haematology and Bone Marrow Transplantation, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel The Wohl Institute for Translational Medicine, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
  • 2 Pediatric Department A and Immunology Service, Jeffrey Modell Foundation Center, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel The Wohl Institute for Translational Medicine, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
  • 3 Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, PA 19111.
  • 4 The Wohl Institute for Translational Medicine, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel Pediatric Gastroenterology and Nutrition Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
  • 5 Pediatric Department A and Immunology Service, Jeffrey Modell Foundation Center, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
  • 6 The Wohl Institute for Translational Medicine, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel Sheba Cancer Research Center, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
  • 7 Imaging Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
  • 8 The Wohl Institute for Translational Medicine, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel Department of Pathology, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
  • 9 Department of Pathology, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
  • 10 The Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
  • 11 Division of Haematology and Bone Marrow Transplantation, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
  • 12 Division of Gastroenterology, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
  • 13 Department of Internal Medicine C, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
  • 14 Pediatric Gastroenterology and Nutrition Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
  • 15 Laboratory of Molecular Medicine, Rambam Health Care Campus and Rappaport Faculty of Medicine and Research Institute, Technion, Haifa 8875361, Israel.
  • 16 Department of Genetics, The Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Edmond Safra Campus, Givat Ram, Jerusalem 9190401, Israel.
  • 17 Division of Haematology and Bone Marrow Transplantation, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel The Wohl Institute for Translational Medicine, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel Sheba Cancer Research Center, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel The Everard and Mina Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 5290002, Israel.
  • 18 Laboratory of Molecular Medicine, Rambam Health Care Campus and Rappaport Faculty of Medicine and Research Institute, Technion, Haifa 8875361, Israel [email protected] [email protected].
  • 19 Pediatric Department A and Immunology Service, Jeffrey Modell Foundation Center, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel The Wohl Institute for Translational Medicine, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel [email protected] [email protected].
PMID: 27432940 DOI: 10.1084/jem.20151618
Abstract

The analysis of individuals with telomere defects may shed LIGHT on the delicate interplay of factors controlling genome stability, premature aging, and Cancer. We herein describe two Coats plus patients with telomere and genomic defects; both harbor distinct, novel mutations in STN1, a member of the human CTC1-STN1-TEN1 (CST) complex, thus linking this gene for the first time to a human telomeropathy. We characterized the patients' phenotype, recapitulated it in a zebrafish model and rescued cellular and clinical aspects by the ectopic expression of wild-type STN1 or by thalidomide treatment. Interestingly, a significant lengthy control of the gastrointestinal bleeding in one of our patients was achieved by thalidomide treatment, exemplifying a successful bed-to-bench-and-back approach.

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