Human T-cell function is dependent on T-cell antigen receptor (TCR) and co-signalling as evidenced by immunodeficiencies affecting TCR-dependent signalling pathways. Here, we show four human patients with EBV+ disseminated smooth muscle tumours that carry two homozygous loss-of-function mutations in the CARMIL2 (RLTPR) gene encoding the capping protein regulator and myosin 1 linker 2. These patients lack regulatory T cells without evidence of organ-specific autoimmunity, and have defective CD28 co-signalling associated with impaired T-cell activation, differentiation and function, as well as perturbed cytoskeletal organization associated with T-cell polarity and migration disorders. Human CARMIL2-deficiency is therefore an autosomal recessive primary immunodeficiency disorder associated with defective CD28-mediated TCR co-signalling and impaired cytoskeletal dynamics.

Measurement of antigliadin antibodies in patients with diabetes mellitus type 1 helped in the selection of patients to undergo jejunal biopsy. Antiendomysial antibodies were highly specific and moderately sensitive in predicting celiac disease. The prevalence of celiac disease was higher in diabetics than in the general population, suggesting the need for regular screening assessment of diabetic children.

ABSTRACT. Infantile myofibromatosis is a rare genetic disorder characterized by the development of benign tumors in the skin, muscle, bone, and viscera. The molecular pathogenesis is still incompletely known. An autosomal dominant form had been reported as causally related with mutations in the gene for platelet-derived growth factor receptor beta (PDGFRB). We report here two siblings with infantile myofibromatosis and with a PDGFRB mutation identified by exome sequence analysis. However, the unaffected mother also had the same PDGFRB mutation. We showed that both children had also inherited from their healthy father a heterozygous mutation in the gene for receptor protein tyrosine phosphatase gamma (PTPRG), an enzyme known to dephosphorylate PDGFRB. We suggest that in this family, the additional mutation in PTPRG may explain the full phenotypic penetrance in the siblings affected, in comparison with the unaffected mother.

RESUMO Na sociedade moderna vive-se, de forma frenética e frequente, um momento de culto e adoração ao corpo. Essa prática é amparada e induzida, sobretudo, pelas mídias. Assim sendo, elas promovem a adesão a uma estética "padrão" e "ideal", incentivando a cultura das cirurgias plásticas, da prática do exercício físico em academias, da venda massiva de cosméticos, bem como de produtos para emagrecer. Como forma de se encaixar nesse padrão estético, muitos sujeitos têm feito o consumo exagerado de substâncias ilegais para alterar este corpo "feio" ou "desproporcional" de forma mais rápida. É um consumo desenfreado que afeta homens, mulheres e adolescentes. Seu principal objetivo é ganhar massa muscular ao mesmo tempo em que trabalham na melhoria do seu rendimento físico por meio, sobretudo, de anabolizantes, uma vez que querem ver os resultados instantaneamente. O uso indiscriminado desses anabolizantes (ou EAA) fazem com que as mais diversas doenças se desenvolvam como consequência deste uso desenfreado de substâncias tóxicas, pois começam a aparecer efeitos adversos ao esperado em relação ao uso das EAA, tais como atrofia do tecido testicular (causando impotência e/ou infertilidade), tumores de próstata e ginecomastia em homens, masculinização (sobretudo alteração na voz), irregularidade menstrual e aumento do clitóris em mulheres e, ainda, em ambos os sexos há a possibilidade do desenvolvimento da calvície, erupções acneicas, aumento da libido, irritabilidade, disfunção hepática e agressividade. Diante deste contexto, o objetivo desta pesquisa foi analisar quais efeitos colaterais foram vivenciados pelos usuários durante e após o uso de EAA e qual o grau de gravidade de cada um dos sintomas apresentados.

Positive AGAA, AGAG or EmA results are probably nonspecific for the presence of celiac disease among autoimmune rheumatologic disease patients. The intake of prednisone and immunosuprressant drugs seems to reduce the prevalence of IgA EmA, but it does not interfere with antigliadin antibodies tests.Further studies are required to estimate more accurately the prevalence of this disease in rheumatologic patients.

Infantile myofibromatosis (IM) is a rare disorder characterized by the development of benign tumors in the skin, muscle, bone, and viscera. The incidence is 1/150,000 live births and the disease is the most common cause of fibrous tumors in infancy. Cases which lack visceral involvement generally have a more benign course, usually with spontaneous regression of the tumors. On the other hand, the prognosis tends to be unfavorable when there is involvement of vital organs, which can lead to significant mortality. The identification of rare variants in genes that may cause IM is the first step towards the possibility of targeted treatments; however, the molecular pathogenesis of IM is poorly understood. In the present study, we report the results of exome sequence analysis of two brothers diagnosed with visceral multicentric infantile myofibromatosis, and their healthy consanguineous parents. In the two brothers we identified novel homozygous variants in NDRG4 gene (N-myc downregulated gene family member 4) and in RLTPR gene (RGD motif, leucine rich repeats, tropomodulin domain and proline-rich containing). The healthy parents were heterozygous for both variants. Consistent with the phenotype of IM, NDRG4 is a tumor-related gene; its expression has been shown to be decreased in numerous tumor types, suggesting that it might be a tumor suppressor gene. Additionally, studies have demonstrated that NDRG4 may have a role in cell survival and tumor invasion. We thus propose that this homozygous variant in NDRG4 may be the causative variant of the autosomal recessive form of IM in the studied family and that it should be investigated in other cases of autosomal recessive infantile myofibromatosis.

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OBJETIVO: Avaliar a prevalência da doença celíaca (DC) em crianças e adolescentes com diabetes melito tipo 1 (DM1) atendidos no Serviço de Endocrinologia Pediátrica do Hospital das Clínicas da Universidade Federal de Minas Gerais. SUJEITOS E MÉTODOS: Incluídos no estudo crianças e adolescentes com diagnóstico prévio de DM1 acompanhadas no serviço no período de março de 1999 a abril de 2009, com idades entre zero e 18 anos. Todos foram rastreados para DC na primeira consulta e anualmente. A investigação foi realizada por meio da dosagem dos anticorpos da classe IgA (AGAA) e IgG (AGAG) antigliadina. Os pacientes com AGAA e/ou AGAG acima de duas vezes o valor de referência foram submetidos à biópsia intestinal. RESULTADOS: Foram excluídos 21 pacientes do total inicial de 384. Destes, 50 tiveram a sorologia positiva e 29 foram submetidos à biópsia intestinal. A prevalência encontrada foi de 3,1%. CONCLUSÃO: O rastreamento periódico da DC nos pacientes diabéticos deve ser encorajado, dada sua alta prevalência.