Huang, ShurongShurongHuangLee, LinLinLeeHanson, Nancy BNancy BHansonLenaerts, CatherineCatherineLenaertsHoehn, HolgerHolgerHoehnPoot, MartinMartinPootRubin, Craig DCraig DRubinChen, Da-FuDa-FuChenCHIH-CHAO YANGJuch, HeikeHeikeJuchDorn, ThomasThomasDornSpiegel, RolandRolandSpiegelOral, Elif AriogluElif AriogluOralAbid, MohammedMohammedAbidBattisti, CarlaCarlaBattistiLucci-Cordisco, EmanuelaEmanuelaLucci-CordiscoNeri, GiovanniGiovanniNeriSteed, Erin HErin HSteedKidd, AlexaAlexaKiddIsley, WilliamWilliamIsleyShowalter, DavidDavidShowalterVittone, Janet LJanet LVittoneKonstantinow, AlexanderAlexanderKonstantinowRing, JohannesJohannesRingMeyer, PeterPeterMeyerWenger, Sharon LSharon LWengervon Herbay, AxelAxelvon HerbayWollina, UweUweWollinaSchuelke, MarkusMarkusSchuelkeHuizenga, Carin RCarin RHuizengaLeistritz, Dru FDru FLeistritzMartin, George MGeorge MMartinMian, I SairaI SairaMianOshima, JunkoJunkoOshima2025-12-122025-12-122006-06https://scholars.lib.ntu.edu.tw/handle/123456789/734560The 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.enjournal article10.1002/humu.2033716673358