The spectrum of WRN mutations in Werner syndrome patients

Shurong Huang, Lin Lee, Nancy B. Hanson, Catherine Lenaerts, Holger Hoehn, Martin Poot, Craig D. Rubin, Da Fu Chen, Chih Chao Yang, Heike Juch, Thomas Dorn, Roland Spiegel, Elif Arioglu Oral, Mohammed Abid, Carla Battisti, Emanuela Lucci-Cordisco, Giovanni Neri, Erin H. Steed, Alexa Kidd, William IsleyDavid Showalter, Janet L. Vittone, Alexander Konstantinow, Johannes Ring, Peter Meyer, Sharon L. Wenger, Axel Von Herbay, Uwe Wollina, Markus Schuelke, Carin R. Huizenga, Dru F. Leistritz, George M. Martin, I. Saira Mian, Junko Oshima

Research output: Contribution to journalArticle

138 Scopus citations

Abstract

The International Registry of Werner syndrome (www.wernersyndrome.org) has been providing molecular diagnosis of the Werner syndrome (WS) for the past decade. The present communication summarizes, from among 99 WS subjects, the spectrum of 50 distinct mutations discovered by our group and by others since the WRN gene (also called RECQL2 or REQ3) was first cloned in 1996; 25 of these have not previously been published. All WRN mutations reported thus far have resulted in the elimination of the nuclear localization signal at the C-terminus of the protein, precluding functional interactions in the nucleus; thus, all could be classified as null mutations. We now report two new mutations in the N-terminus that result in instability of the WRN protein. Clinical data confirm that the most penetrant phenotype is bilateral ocular cataracts. Other cardinal signs were seen in more than 95% of the cases. The median age of death, previously reported to be in the range of 46-48 years, is 54 years. Lymphoblastoid cell lines (LCLs) have been cryopreserved from the majority of our index cases, including material from nuclear pedigrees. These, as well as inducible and complemented hTERT (catalytic subunit of human telomerase) immortalized skin fibroblast cell lines are available to qualified investigators.

Original languageEnglish (US)
Pages (from-to)558-567
Number of pages10
JournalHuman mutation
Volume27
Issue number6
DOIs
StatePublished - Jun 1 2006

Keywords

  • Aging
  • International registries
  • Penetrance
  • Progeroid syndromes
  • RECQ3
  • RECQL2
  • RecQ helicases
  • WRN
  • Werner helicase
  • Werner syndrome

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Huang, S., Lee, L., Hanson, N. B., Lenaerts, C., Hoehn, H., Poot, M., Rubin, C. D., Chen, D. F., Yang, C. C., Juch, H., Dorn, T., Spiegel, R., Oral, E. A., Abid, M., Battisti, C., Lucci-Cordisco, E., Neri, G., Steed, E. H., Kidd, A., ... Oshima, J. (2006). The spectrum of WRN mutations in Werner syndrome patients. Human mutation, 27(6), 558-567. https://doi.org/10.1002/humu.20337