A mutation creating an out-of-frame alternative translation initiation site in the GRHPR 5'UTR causing primary hyperoxaluria type II.

Primary hyperoxaluria type II is a recessive genetic disorder caused by mutations in the GRHPR gene. Although several dozen mutations have been described, all affect coding or transcript splicing. A man suspected of having primary hyperoxaluria type II was heterozygous for a novel single-nucleotide deletion (c.694delC) in GRHPR affecting Gln(232) , which introduced a pre-mature termination (p.Gln232Argfs*3). Two 5'untranslated region (UTR) variants of unknown significance were also noted. We show that these two variants occur in cis, on the opposite allele, and introduce - immediately upstream of the canonical translation initiation site - a novel out-of-frame translational start site. In vitro studies using the GRHPR 5'UTR fused to a luciferase reporter show that the variant start site pre-empted initiation at the canonical translational start site, and this was corroborated within the broader context of 1.3 kb of the GRHPR proximal promoter. This latter mechanism may be underappreciated in general; reports of clinically significant functional variation of this type are extremely rare.

Survey of first-year medical students to assess their knowledge and attitudes toward organ transplantation and donation.

BACKGROUND: The important shortage of organ donors is still a fundamental public health problem in France. Improving the knowledge and attitudes of health care professionals could help to promote organ donation. The aim of this survey was to evaluate the level of knowledge of medical students and their gaps about organ donation prior to any medical course. MATERIALS AND METHODS: A survey was conducted among 571 first-year medical students at a medical faculty in Lyon. Their knowledge, attitudes, personal views, and perceptions toward organ donation and transplantation were investigated prior to any medical course. A 31-item anonymous questionnaire including queries about personal views of organ donation, factual knowledge, and awareness of French law was distributed to the students. RESULTS: To "willingness to donate a kidney to a relative," 97.7% of respondents consented, 0.9% objected, and 1.4% did not answer. Their attitudes toward cadaveric organ donation were different: 81.1% agreed, 13.5% refused, and 5.4% did not answer. Regarding their knowledge about which organs could be transplanted, 95% of the respondents were aware of the possibility to transplant a face and 14% thought that xenotransplantation was performed nowadays. CONCLUSIONS: First-year medical students have a good knowledge level regarding the organ donation and transplantation system prior to their medical course. Some gaps remain which could be improved. The results of this study supported a greater emphasis on providing information regarding transplantation in medical schools to improve the knowledge of future health care professionals. A follow-up survey of the participants at the end of their medical course will be interesting to assess the progress of their attitudes.

New treatment strategies for proliferative lupus nephritis: keep children in mind!

Renal involvement is frequent in children with systemic lupus erythematosus (SLE) and carries significant short and long-term morbidity. Treatment strategy in proliferative glomerulonephritis relies mainly on studies in adult patients where conventional treatment regimens including high doses of cyclophosphamide (CYC) and steroids may cause severe side effects. New strategies including sequential therapies of various combinations of low dose CYC, calcineurine inhibitors (cyclosporine or tacrolimus), mycophenolate mofetil, azathioprine, rituximab are now under investigation in adult patients with very few data in children. Organization of international registries and controlled trials in children with lupus nephritis is mandatory to determine long term prognosis and to validate less toxic therapy regimens in childhood.