The spectrum of WRN mutations in Werner syndrome patients.
Journal
Human Mutation
Journal Volume
27
Journal Issue
6
Start Page
558
End Page
567
ISSN
10597794
Date Issued
2006-06
Author(s)
Huang, Shurong
Lee, Lin
Hanson, Nancy B
Lenaerts, Catherine
Hoehn, Holger
Poot, Martin
Rubin, Craig D
Chen, Da-Fu
Juch, Heike
Dorn, Thomas
Spiegel, Roland
Oral, Elif Arioglu
Abid, Mohammed
Battisti, Carla
Lucci-Cordisco, Emanuela
Neri, Giovanni
Steed, Erin H
Kidd, Alexa
Isley, William
Showalter, David
Vittone, Janet L
Konstantinow, Alexander
Ring, Johannes
Meyer, Peter
Wenger, Sharon L
von Herbay, Axel
Wollina, Uwe
Schuelke, Markus
Huizenga, Carin R
Leistritz, Dru F
Martin, George M
Mian, I Saira
Oshima, Junko
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.
Publisher
Hindawi Limited
Type
journal article