Absent B cells, agammaglobulinemia, and hypertrophic cardiomyopathy in folliculin-interacting protein 1 deficiency

Agammaglobulinemia is the most profound primary antibody deficiency that can occur due to an early termination of B-cell development. We here investigated 3 novel patients, including the first known adult, from unrelated families with agammaglobulinemia, recurrent infections, and hypertrophic cardiomyopathy (HCM). Two of them also presented with intermittent or severe chronic neutropenia. We identified homozygous or compound-heterozygous variants in the gene for folliculin interacting protein 1 (FNIP1), leading to loss of the FNIP1 protein. B-cell metabolism, including mitochondria! numbers and activity and phosphatidylinositol 3-kinase/AKT pathway, was impaired. These defects recapitulated the Fnip1(-/-) animal model. Moreover, we identified either uniparental disomy or copy-number variants (CNVs) in 2 patients, expanding the variant spectrum of this novel inborn error of I immunity. The results indicate that FNIP1 deficiency can be caused by complex genetic mechanisms and support the clinical utility of exome sequencing and CNV analysis in patients with broad phenotypes, including agammaglobulinemia and HCM. FNIP1 deficiency is a novel inborn error of immunity characterized by early and severe B-cell development defect, agammaglobulinemia, variable neutropenia, and HCM. Our findings elucidate a functional and relevant role of FNIP1 in B-cell development and metabolism and potentially neutrophil activity.Molecular Technology and Informatics for Personalised Medicine and Healt

Clinical studies in non-chromosome 4-linked facioscapulohumeral muscular dystrophy

Item does not contain fulltex

Size does matter, but not only size: Two alternative dispersal strategies for viviparous mangrove propagules

We studied the propagules of two widespread mangrove species, Ceriops tagal and Rhizophora mucronata, that are similar in shape but differ in other morpho-anatomical features (average length is 23.1±2.2cm and 44.4±4.3cm, resp. n=180). We hypothesized the propagules of both species to have a different hydrodynamic behavior and establishing capacity, resulting in a different dispersal strategy. More specifically, we hypothesized that C. tagal propagules have a larger dispersal capacity than those of R. mucronata. The dispersal strategies of C. tagal and R. mucronata propagules were elucidated through a combination of a propagule tracking (n=180 per species), predation (n=20 per species) and root-growth experiment (n=120 per species), carried out in the field. C. tagal and R. mucronata adopted two different dispersal strategies. C. tagal releases a large number of propagules and disperses fast, having a slender morphology and low density (average ρ: 985.29±19.02gL -1), as well as a high agility (smaller size) when dispersing through dense root systems. C. tagal propagules have a theoretical advantage to disperse over longer distances over the thicker, longer and denser R. mucronata propagules (average ρ: 1003.92±8.52gL -1; t=8.90, p<0.0001, n=197). C. tagal have, however, lower establishment chances due to slower root-growth, desiccation sensitivity and smaller size. In contrast to Ceriops' tactic of releasing high numbers of propagules and fast dispersal, R. mucronata has adopted a dispersal tactic of survival. Fewer propagules are released, but they are more resistant to predators due to their larger size and they can anchor themselves faster due to quicker root-growth (Mann-Whitney U: p<0.0001, n Ct=59, n Rm=57). Overall, propagule characteristics of both species result in different and alternative dispersal strategies on a local scale, contradicting our initial hypothesis. On a global scale, we hypothesize this might lead to a similar capacity for long-distance dispersal, ending in successful establishment. © 2012 Elsevier B.V.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Affinity and diversity indices for anopheline immature forms Afinidade e diversidade de formas imaturas de anofelinos

As for the entire Amazon Region, malaria continues to be a major health public problem in Roraima that presented an Annual Parasitic Index of 85.4 in 2005, the highest in Brazil. Information on anopheline breeding sites is an essential component in malaria control strategies. Aiming to contribute to the limited knowledge on anopheline immature forms in Roraima, collections and breeding site observations were performed in 10 breeding sites around the capital city Boa Vista. Collections were carried out in the rainy and dry season periods between April 2004 and January 2005. Breeding sites comprised natural and artificial water reservoirs. A total of 623 immature forms were collected belonging to Anopheles albitarsis s.l., An.triannulatus s.l., An. nuneztovari/dunhami, An. braziliensis, An. evansae, An. oswaldoi s.l., An. strodei and An. darlingi. An. albitarsis and An. braziliensis were the most frequently found species. Eight larvae of An. darlingi were found in only one breeding site located in the forest. An. triannulatus/An. nuneztovari and An. albitarsis/An. braziliensis were the pairs of species that mostly occurred together. Both pair of species displayed the highest affinity index what might indicate a high compatibility for the same breeding conditions and/or a synergistic co-occurrence. Species diversity index was higher for the dry season.<br>Como para toda a Amazônia, a malária representa um importante problema de saúde pública em Roraima. Roraima apresentou um índice parasitário anual de 85,4 em 2005, o maior do Brasil. O conhecimento dos criadouros de anofelinos constitui-se num componente primordial nas estratégias de controle da malária. No intuito de contribuir para o limitado conhecimento dos criadouros de anofelinos em Roraima, coleções de imaturos e observações dos criadouros foram realizadas no entorno da capital Boa Vista. As coletas foram feitas nas estações seca e chuvosa entre abril de 2004 e janeiro de 2005. Os criadouros observados foram reservatórios de água naturais e artificiais. Um total de 623 formas imaturas foram coletadas pertencentes às espécies An. albitarsis s.l., An.triannulatus s.l., An. nuneztovari/dunhami, An. braziliensis, An. evansae, An. oswaldoi s.l., An. strodei e An. darlingi. An. braziliensis e An. albitarsis foram as espécies mais freqüentemente encontradas. Oito larvas de An. darlingi foram encontradas em apenas um criadouro na floresta. An. triannulatus/An. nuneztovari e An. albitarsis/An. braziliensis foram os pares de espécies de maior co-ocorrência. Ambos pares de espécies apresentaram o maior índice de afinidade o que pode indicar compatibilidade para as mesmas condições prevalentes nos criadouros e/ou sinergismo. O índice de diversidade de espécies foi maior para a estação seca