title: Mutations in STN1 cause Coats plus syndrome and are associated with genomic and telomere defects.
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.
authors.affiliation: 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.
authors.forename: Amos J
authors.initials: AJ
authors.lastname: Simon
authors.affiliation: 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.
authors.forename: Atar
authors.initials: A
authors.lastname: Lev
authors.affiliation: Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, PA 19111.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Batia
authors.initials: B
authors.lastname: Weiss
authors.affiliation: 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.
authors.forename: Anna
authors.initials: A
authors.lastname: Rylova
authors.affiliation: 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.
authors.forename: Eran
authors.initials: E
authors.lastname: Eyal
authors.affiliation: 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.
authors.forename: Nitzan
authors.initials: N
authors.lastname: Kol
authors.affiliation: 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.
authors.forename: Ortal
authors.identifier: 0000-0003-1168-9758
authors.initials: O
authors.lastname: Barel
authors.affiliation: 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.
authors.forename: Keren
authors.initials: K
authors.lastname: Cesarkas
authors.affiliation: 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.
authors.forename: Michalle
authors.identifier: 0000-0001-5269-4196
authors.initials: M
authors.lastname: Soudack
authors.affiliation: Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, PA 19111.
authors.forename: Noa
authors.identifier: 0000-0002-9013-9537
authors.initials: N
authors.lastname: Greenberg-Kushnir
authors.affiliation: Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, PA 19111.
authors.forename: Michele
authors.initials: M
authors.lastname: Rhodes
authors.affiliation: Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, PA 19111.
authors.forename: David L
authors.identifier: 0000-0002-0792-3188
authors.initials: DL
authors.lastname: Wiest
authors.affiliation: 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.
authors.forename: Ginette
authors.initials: G
authors.lastname: Schiby
authors.affiliation: Department of Pathology, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
authors.forename: Iris
authors.initials: I
authors.lastname: Barshack
authors.affiliation: 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.
authors.forename: Shulamit
authors.initials: S
authors.lastname: Katz
authors.affiliation: The Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
authors.forename: Elon
authors.identifier: 0000-0001-8094-7429
authors.initials: E
authors.lastname: Pras
authors.affiliation: The Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
authors.forename: Hana
authors.identifier: 0000-0003-2815-9008
authors.initials: H
authors.lastname: Poran
authors.affiliation: The Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
authors.forename: Haike
authors.initials: H
authors.lastname: Reznik-Wolf
authors.affiliation: Division of Haematology and Bone Marrow Transplantation, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
authors.forename: Elena
authors.initials: E
authors.lastname: Ribakovsky
authors.affiliation: Division of Gastroenterology, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
authors.forename: Carlos
authors.initials: C
authors.lastname: Simon
authors.affiliation: Department of Internal Medicine C, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
authors.forename: Wadi
authors.initials: W
authors.lastname: Hazou
authors.affiliation: Department of Internal Medicine C, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
authors.forename: Yechezkel
authors.identifier: 0000-0001-7781-6153
authors.initials: Y
authors.lastname: Sidi
authors.affiliation: 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.
authors.forename: Avishay
authors.identifier: 0000-0002-4642-0399
authors.initials: A
authors.lastname: Lahad
authors.affiliation: Laboratory of Molecular Medicine, Rambam Health Care Campus and Rappaport Faculty of Medicine and Research Institute, Technion, Haifa 8875361, Israel.
authors.forename: Hagar
authors.initials: H
authors.lastname: Katzir
authors.affiliation: Laboratory of Molecular Medicine, Rambam Health Care Campus and Rappaport Faculty of Medicine and Research Institute, Technion, Haifa 8875361, Israel.
authors.forename: Shira
authors.initials: S
authors.lastname: Sagie
authors.affiliation: Department of Genetics, The Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Edmond Safra Campus, Givat Ram, Jerusalem 9190401, Israel.
authors.forename: Haifa A
authors.identifier: 0000-0001-5971-0005
authors.initials: HA
authors.lastname: Aqeilan
authors.affiliation: Department of Genetics, The Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Edmond Safra Campus, Givat Ram, Jerusalem 9190401, Israel.
authors.forename: Galina
authors.identifier: 0000-0001-6779-8385
authors.initials: G
authors.lastname: Glousker
authors.affiliation: 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.
authors.forename: Ninette
authors.initials: N
authors.lastname: Amariglio
authors.affiliation: Department of Genetics, The Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Edmond Safra Campus, Givat Ram, Jerusalem 9190401, Israel.
authors.forename: Yehuda
authors.identifier: 0000-0001-7720-435X
authors.initials: Y
authors.lastname: Tzfati
authors.affiliation: Laboratory of Molecular Medicine, Rambam Health Care Campus and Rappaport Faculty of Medicine and Research Institute, Technion, Haifa 8875361, Israel seligs@tx.technion.ac.il raz.somech@sheba.health.gov.il.
authors.forename: Sara
authors.identifier: 0000-0001-5759-9948
authors.initials: S
authors.lastname: Selig
authors.affiliation: 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.
authors.forename: Gideon
authors.initials: G
authors.lastname: Rechavi
authors.affiliation: 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 seligs@tx.technion.ac.il raz.somech@sheba.health.gov.il.
authors.forename: Raz
authors.initials: R
authors.lastname: Somech
mesh_terms: D000818:Animals; D001259:Ataxia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002114:Calcinosis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020863:Central Nervous System Cysts / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D056784:Leukoencephalopathies / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D009128:Muscle Spasticity / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D012164:Retinal Diseases / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012640:Seizures / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016615:Telomere / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D034501:Telomere-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D013792:Thalidomide / Q000008:administration & dosage* / Q000009:adverse effects; D015027:Zebrafish
chemical_list: C544946:Stn1 protein, human; D034501:Telomere-Binding Proteins; D013792:Thalidomide