PUBLICATION

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

Authors
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.
ID
ZDB-PUB-160721-4
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.
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.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping