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 Ribakovsky, Carlos 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

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.