ZFIN ID: ZDB-PUB-160721-4
Mutations in STN1 cause Coats plus syndrome and are associated with genomic and telomere defects
Simon, A.J., Lev, A., Zhang, Y., Weiss, B., Rylova, A., Eyal, E., Kol, N., Barel, O., Cesarkas, K., Soudack, M., Greenberg-Kushnir, N., Rhodes, M., Wiest, D.L., Schiby, G., Barshack, I., Katz, S., Pras, E., Poran, H., Reznik-Wolf, H., Ribakovsky, E., Simon, C., Hazou, W., Sidi, Y., Lahad, A., Katzir, H., Sagie, S., Aqeilan, H.A., Glousker, G., Amariglio, N., Tzfati, Y., Selig, S., Rechavi, G., Somech, R.
Date: 2016
Source: The Journal of experimental medicine 213(8): 1429-40 (Journal)
Registered Authors: Zhang, Yong
Keywords: none
MeSH Terms:
  • Animals
  • Ataxia*/drug therapy
  • Ataxia*/genetics
  • Ataxia*/metabolism
  • Ataxia*/pathology
  • Brain Neoplasms*/drug therapy
  • Brain Neoplasms*/genetics
  • Brain Neoplasms*/metabolism
  • Brain Neoplasms*/pathology
  • Calcinosis*/drug therapy
  • Calcinosis*/genetics
  • Calcinosis*/metabolism
  • Calcinosis*/pathology
  • Central Nervous System Cysts*/drug therapy
  • Central Nervous System Cysts*/genetics
  • Central Nervous System Cysts*/metabolism
  • Central Nervous System Cysts*/pathology
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation/drug effects*
  • Humans
  • Leukoencephalopathies*/drug therapy
  • Leukoencephalopathies*/genetics
  • Leukoencephalopathies*/metabolism
  • Leukoencephalopathies*/pathology
  • Male
  • Muscle Spasticity*/drug therapy
  • Muscle Spasticity*/genetics
  • Muscle Spasticity*/metabolism
  • Muscle Spasticity*/pathology
  • Mutation*
  • Retinal Diseases*/drug therapy
  • Retinal Diseases*/genetics
  • Retinal Diseases*/metabolism
  • Retinal Diseases*/pathology
  • Seizures*/drug therapy
  • Seizures*/genetics
  • Seizures*/metabolism
  • Seizures*/pathology
  • Telomere*/genetics
  • Telomere*/metabolism
  • Telomere*/pathology
  • Telomere-Binding Proteins*/biosynthesis
  • Telomere-Binding Proteins*/genetics
  • Thalidomide/administration & dosage*
  • Thalidomide/adverse effects
  • Zebrafish
PubMed: 27432940 Full text @ J. Exp. Med.
FIGURES
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.
ADDITIONAL INFORMATIONNo data available