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

Amos J. Simon, Atar Lev, Yong Zhang, Batia Weiss, Anna Rylova, Eran Eyal, Nitzan Kol, Ortal Barel, Keren Cesarkas, Michalle Soudack, Noa Greenberg-Kushnir, Michele Rhodes, David L. Wiest, Ginette Schiby, Iris Barshack, Shulamit Katz, Elon Pras, Hana Poran, Haike Reznik-Wolf, Elena RibakovskyCarlos Simon, Wadi Hazou, Yechezkel Sidi, Avishay Lahad, Hagar Katzir, Shira Sagie, Haifa A. Aqeilan, Galina Glousker, Ninette Amariglio, Yehuda Tzfati, Sara Selig*, Gideon Rechavi, Raz Somech

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1429-1440
Number of pages12
JournalJournal of Experimental Medicine
Volume213
Issue number8
DOIs
StatePublished - 25 Jul 2016

Funding

FundersFunder number
Ernest and Bonnie Beutler Research Program
Israeli Centers of Excellence
Kahn Family Foundation
Sagol Neuroscience Network
Teva National Network of Excellence in Neuroscience
National Institutes of HealthR21AI111208
National Cancer InstituteP30CA006927
Jeffrey Modell Foundation
Israel Cancer Research Fund
Worldwide Cancer Research15-0338
Israel Science Foundation41/11, 883/12, 1729/13, 1796/12
Tel Aviv University1667/12
Israeli Centers for Research Excellence

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