The spectrum ofWRNmutations in Werner syndrome patients
| Autor: | Erin H. Steed, Craig D. Rubin, Markus Schuelke, A. Konstantinow, William L. Isley, Junko Oshima, Lin Lee, Mohammed Abid, Chih-Chao Yang, Nancy B. Hanson, Emanuela Lucci-Cordisco, George M. Martin, Peter Meyer, Axel von Herbay, Da Fu Chen, Thomas Dorn, I. Saira Mian, Alexa Kidd, Sharon L. Wenger, Janet L. Vittone, Uwe Wollina, Johannes Ring, Carin R. Huizenga, Heike Juch, Catherine Lenaerts, Dru F. Leistritz, David Showalter, Roland Spiegel, Carla Battisti, Shurong Huang, Martin Poot, Elif A. Oral, Holger Hoehn, Giovanni Neri |
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| Rok vydání: | 2006 |
| Předmět: |
Adult
Models Molecular Werner Syndrome Helicase DNA Mutational Analysis Molecular Sequence Data Biology Article Progeroid syndromes Cataracts Genetics medicine Humans Telomerase reverse transcriptase Amino Acid Sequence Registries education Gene Genetics (clinical) Aged Werner syndrome Aged 80 and over education.field_of_study RecQ Helicases DNA Helicases Middle Aged medicine.disease Penetrance Phenotype Pedigree Exodeoxyribonucleases Werner Syndrome Sequence Alignment |
| Zdroj: | Human Mutation. 27:558-567 |
| ISSN: | 1098-1004 1059-7794 |
| DOI: | 10.1002/humu.20337 |
| Popis: | 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. Published 2006 Wiley-Liss, Inc.† |
| Databáze: | OpenAIRE |
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