Suchergebnisse

Neurofibromatosis type 1 (NF1) (von Recklinghausen's disease) is one of the most common human autosomal dominant disorders. In a survey of 374440 17 year old Jewish recruits for military service, 390 cases of NF1 were discovered, with a prevalence of 1.04/1000 (0.94/1000 for males and 1.19/1000 for females), or two to five times the reported prevalence of this disease. NF1 was more common in youngsters whose parents were of North African and Asian origin (1.81/1000 and 0.95/1000, respectively) and less common in those of European and North American origin (0.64/1000). All these differences were statistically significant and may be partially explained by the more advanced parental age of the NF group (as suggested by the larger number of children in the North African and Asian families) or by founder effect or both. The height and weight of the NF1 subjects was significantly lower than those of the controls. The intelligence score of persons with NF1 was similar to that of the control group when corrected for gender and ethnic origin. No significant increase in epilepsy or mental illnesses was found. This study provides evidence of the high overall prevalence of NF1 among Jews in Israel, with significantly increased prevalence in certain ethnic groups.

Abstract The cytokines controlling the development of human interleukin (IL) 17--producing T helper cells in vitro have been difficult to identify. We addressed the question of the development of human IL-17--producing T helper cells in vivo by quantifying the production and secretion of IL-17 by fresh T cells ex vivo, and by T cell blasts expanded in vitro from patients with particular genetic traits affecting transforming growth factor (TGF) beta, IL-1, IL-6, or IL-23 responses. Activating mutations in TGFB1, TGFBR1, and TGFBR2 (Camurati-Engelmann disease and Marfan-like syndromes) and loss-of-function mutations in IRAK4 and MYD88 (Mendelian predisposition to pyogenic bacterial infections) had no detectable impact. In contrast, dominant-negative mutations in STAT3 (autosomal-dominant hyperimmunoglobulin E syndrome) and, to a lesser extent, null mutations in IL12B and IL12RB1 (Mendelian susceptibility to mycobacterial diseases) impaired the development of IL-17--producing T cells. These data suggest that IL-12Rbeta1- and STAT-3--dependent signals play a key role in the differentiation and/or expansion of human IL-17-producing T cell populations in vivo. ; The Laboratory of Human Genetics of Infectious Diseases is supported by the Agence Nationale de la Recherche, the Programme Hospitalier de Recherche Clinique, the European Union (grant LHSP-CT-2005-018736), the BNP Paribas Foundation, the March of Dimes, the Dana Foundation, and the Candi'Oser Association. L. de Beaucoudrey is supported by the Fondation pour la Recherche Medicale as part of the PhD program of Pierre et Marie Curie University. J.L. Casanova is an International Scholar of the Howard Hughes Medical Institute.