Heterogeneity among patients with tumor necrosis factor receptor-associated periodic syndrome phenotypes.

OBJECTIVE: To investigate the prevalence of tumor necrosis factor receptor-associated periodic syndrome (TRAPS) among outpatients presenting with recurrent fevers and clinical features consistent with TRAPS. METHODS: Mutational screening was performed in affected members of 18 families in which multiple members had symptoms compatible with TRAPS and in 176 consecutive subjects with sporadic (nonfamilial) "TRAPS-like" symptoms. Plasma concentrations of soluble tumor necrosis factor receptor superfamily 1A (sTNFRSF1A) were measured, and fluorescence-activated cell sorter analysis was used to measure TNFRSF1A shedding from monocytes. RESULTS: Eight novel and 3 previously reported TNFRSF1A missense mutations were identified, including an amino acid deletion (Delta D42) in a Northern Irish family and a C70S mutation in a Japanese family, both reported for the first time. Only 3 TNFRSF1A variants were found in patients with sporadic TRAPS (4 of 176 patients). Evidence for nonallelic heterogeneity in TRAPS-like conditions was found: 3 members of the "prototype familial Hibernian fever" family did not possess C33Y, present in 9 other affected members. Plasma sTNFRSF1A levels were low in TRAPS patients in whom renal amyloidosis had not developed, but also in mutation-negative symptomatic subjects in 4 families, and in 14 patients (8%) with sporadic TRAPS. Reduced shedding of TNFRSF1A from monocytes was demonstrated in vitro in patients with the T50M and T50K variants, but not in those with other variants. CONCLUSION: The presence of TNFRSF1A shedding defects and low sTNFRSF1A levels in 3 families without a TNFRSF1A mutation indicates that the genetic basis among patients with "TRAPS-like" features is heterogeneous. TNFRSF1A mutations are not commonly associated with nonfamilial recurrent fevers of unknown etiology.

The Genetic Counseling Workplace-An Australasian Perspective. A National Study of Workplace Issues for Genetic Counselors and Associate Genetic Counselors.

Genetic counseling in Australasia (Australia and New Zealand) has been recognized as a profession since the 1980s and has steadily expanded over the past 20 years. The demography of major cities with metropolitan sprawl and sparsely populated rural areas has led to the establishment of 3 types of genetics units: main units in cities, metropolitan outreach, and rural outreach units. A questionnaire was developed to obtain information about the needs, resources, and day-to-day operation of the genetic counselors. The questionnaire addressed the areas of resource availability, professional development, responsibility of genetic counselors in the clinical setting, and their involvement in promotion of the service and public education. Differences observed between the 3 settings in all of these areas included large clinical loads for metropolitan outreach counselors, varying responsibilities in the clinical setting, and a lack of support and resources for rural outreach counselors. Australasian Genetic counselors were found to have a significant interest in developing mechanisms for supervision and were keenly interested in maintaining credentials and professional role development. The results of this study allows genetic counselors themselves to have a better understanding of the roles of their colleagues in the different units; they can also be used by service providers in establishing and supporting genetic counselors, and identifying inequalities and deficiencies in the different practice areas.