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.

Purpose To assess the impact of a multi-modal interdisciplinary course in genetic cancer risk assessment (GCRA) and research collaboration for community-based clinicians. Clinicians are increasingly requested to conduct GCRA, but many are inadequately prepared to provide these services. Methods A prospective analysis of 131 participants (48 physicians, 41 advanced-practice nurses and 42 genetic counselors) from community settings across the U.S. The course was delivered in three phases: distance didactic learning, face-to-face training and 12 months of Web-based professional development activities to support integration of skills into practice. Cancer genetics knowledge, skills, professional self-efficacy and practice changes were measured at baseline, immediate- and 14-months-post course. Results Knowledge, skills and self-efficacy scores were significantly different between practice disciplines; however, post scores increased significantly overall and for each discipline (p<.001). Fourteen-month practice outcomes reflect significant increases in provision of GCRA services (p=.018), dissemination of cancer prevention information (p=.005) and high-risk screening recommendations (p=.004) to patients, patient enrollment in research (p=.013), and educational outreach about GCRA (p=.003). Conclusions Results support the efficacy of the multi-modal course as a tool to develop a genetically literate workforce. Sustained alumni participation in Web-based professional development activities has evolved into a distance-mediated Community of Practice in clinical cancer genetics, modeling the lifelong learning goals envisioned by leading CME stakeholders.

Previous studies have documented that concerns about genetic discrimination (GD) may influence access to and participation in medically necessary care. We sought to characterize how GD issues influence current cancer genetics professional (CGP) practice, determine if their attitudes regarding GD have changed over time, and compare their knowledge and attitudes regarding laws prohibiting GD to a contemporary cohort of non-genetics clinicians. Members of the National Society of Genetic Counselors Familial Cancer Special Interest Group were invited to complete a 39 item online survey, adapted from previously published instruments. The resulting data were compared to a survey of CGPs published in 2000 and to a contemporary cohort of non-genetics clinicians (n = 1,181). There were 153 qualified respondents. Compared to the historical CGP cohort (n = 163), a significantly greater proportion said they would bill insurance for the cost of genetic testing for themselves (P < 0.0001). Most CGPs (94%) considered the risk of GD to be low to theoretical, concordant with 64% who expressed confidence in existing federal laws prohibiting GD. The mean knowledge score of CGPs regarding GD protective laws was significantly greater than that of non-genetics clinicians (P < 0.001). As barometers of change, CGPs show a migration in opinion over the past 8 years, with decreased fear of GD and greater knowledge of laws prohibiting GD compared to non-genetics clinicians. Better knowledge of GD and protective legislation, may facilitate non-genetics clinician utilization of genetics and personalized medicine.

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