Genotype-phenotype correlation in Italian patients with epidermolysis bullosa dystrophica

Dystrophic epidermolysis bullosa (DEB) is a rare skin disorder that is clinically heterogeneous and is transmitted either in dominant (DDEB) or recessive (RDEB) mode. Nevertheless, all variants of DEB are caused by mutations in type VII collagen gene (COL7A1). We report an analysis of COL7A1 mutations in 51 Italian DEB patients, 27 affected with Hallopeau–Siemens RDEB, 19 with non Hallopeau–Siemens RDEB, two with DDEB, two with pretibial RDEB, and one with inversa RDEB. Forty-one mutations were identified, 18 of which are novel. Mutation consequences were analyzed at the mRNA and protein level and genotype–phenotype correlation was determined. Recessive inheritance of a new case of pretibial RDEB was also established. In RDEB patients, six recurrent mutations were identified: 7344GA, 425AG, 8441–14del21, 4783–1GA, 497insA, and G1664A, the last three being found only in Italian patients. Indeed, haplotype analysis supported propagation of ancestral mutated alleles within the Italian population for these particular mutations. Altogether recurrent mutations account for approximately 43% of RDEB alleles in Italian patients and therefore new DEB patients should first be screened for the presence of these mutations

Curva de referência para a medida da translucência nucal na população capixaba Reference range curve of nuchal translucency in the population of the State of Espírito Santo, Brazil

OBJETIVO: Estudar o comportamento da medida da translucência nucal (TN) na população capixaba, no período entre a 10ª e a 14ª semanas de gestação. MATERIAIS E MÉTODOS: Estudou-se de forma transversal 853 fetos, consecutivamente, que apresentaram cariótipos ou fenótipos normais. Todos os fetos foram submetidos, durante a ultra-sonografia de rotina, à medida da TN. A análise estatística utilizou o teste "t" de Student e ANOVA. O teste de regressão ajustou o melhor modelo matemático para traduzir o comportamento da TN. RESULTADOS: A idade materna variou de 14 a 49 anos (média de 30,2 anos), sendo que 22,1% encontravam-se com mais de 35 anos. A TN mostrou comportamento crescente com a idade gestacional e o comprimento cabeça-nádegas (CCN). Houve 73 casos (6,46%) de fetos normais com TN maior que 2,5 mm. O melhor modelo matemático encontrado para representar o comportamento da TN foi a regressão linear simples (TN = 0,414 + 0,020 × CCN), que permitiu estabelecer curva de normalidade com os percentis 5, 10, 25, 50, 75, 90 e 95. CONCLUSÃO: A TN apresenta comportamento crescente com o avançar da idade gestacional, no período de 10 a 14 semanas. A população capixaba apresenta medidas de TN semelhantes às demais populações já testadas.<br>OBJECTIVE: To assess the behavior of nuchal translucency (NT) in the population of the State of Espírito Santo, Brazil, during weeks 10 to 14 of pregnancy and to establish a reference range for this population. MATERIALS AND METHODS: A transversal study was performed in 853 fetuses which presented normal cariotype or phenotype. All the fetuses were submitted to ultrasound analysis for NT measurement, during routine ultrasound examinations. The Student's "t" test and ANOVA were used in the statistical analysis. The regression test was used to adjust the better mathematical model to translate the NT behavior. RESULTS: Maternal age varied between 14 to 49 years (mean 30.2%), and 22.1% were above 35 years of age. The NT measurement increased with gestational age and the crown-rump length (CRL). In 73 normal fetuses (6.46%) the NT was thicker than 2.5 mm. The better mathematical model was the linear correlation (NT = 0.414 + 0.020 × CRL) which allowed to establish the reference range (percentiles 5, 10, 25, 50, 75, 90 and 95). CONCLUSION: The NT measurement is a manageable method during the usual ultrasonography. NT measurements increase with gestational age during weeks 10 to 14 of pregnancy. The NT measurements seen in the population of the State of Espírito Santo were similar to other population tested

Tissue-specific and SRSF1-dependent splicing of fibronectin, a matrix protein that controls host cell invasion.

Cell invasion targets specific tissues in physiological placental implantation and pathological metastasis, which raises questions about how this process is controlled. We compare dermis and endometrium capacities to support trophoblast invasion, using matching sets of human primary fibroblasts in a coculture assay with human placental explants. Substituting endometrium, the natural trophoblast target, with dermis dramatically reduces trophoblast interstitial invasion. Our data reveal that endometrium expresses a higher rate of the fibronectin (FN) extra type III domain A+ (EDA+) splicing isoform, which displays stronger matrix incorporation capacity. We demonstrate that the high FN content of the endometrium matrix, and not specifically the EDA domain, supports trophoblast invasion by showing that forced incorporation of plasma FN (EDA-) promotes efficient trophoblast invasion. We further show that the serine/arginine-rich protein serine/arginine-rich splicing factor 1 (SRSF1) is more highly expressed in endometrium and, using RNA interference, that it is involved in the higher EDA exon inclusion rate in endometrium. Our data therefore show a mechanism by which tissues can be distinguished, for their capacity to support invasion, by their different rates of EDA inclusion, linked to their SRSF1 protein levels. In the broader context of cancer pathology, the results suggest that SRSF1 might play a central role not only in the tumor cells, but also in the surrounding stroma

Coronavirus and paramyxovirus in bats from Northwest Italy

Background: Bat-borne virus surveillance is necessary for determining inter-species transmission risks and is important due to the wide-range of bat species which may harbour potential pathogens. This study aimed to monitor coronaviruses (CoVs) and paramyxoviruses (PMVs) in bats roosting in northwest Italian regions. Our investigation was focused on CoVs and PMVs due to their proven ability to switch host and their zoonotic potential. Here we provide the phylogenetic characterization of the highly conserved polymerase gene fragments. Results: Family-wide PCR screenings were used to test 302 bats belonging to 19 different bat species. Thirty-eight animals from 12 locations were confirmed as PCR positive, with an overall detection rate of 12.6% [95% CI: 9.3–16.8]. CoV RNA was found in 36 bats belonging to eight species, while PMV RNA in three Pipistrellus spp. Phylogenetic characterization have been obtained for 15 alpha- CoVs, 5 beta-CoVs and three PMVs; moreover one P. pipistrellus resulted co-infected with both CoV and PMV. A divergent alpha-CoV clade from Myotis nattereri SpA is also described. The compact cluster of beta-CoVs from R. ferrumequinum roosts expands the current viral sequence database, specifically for this species in Europe. To our knowledge this is the first report of CoVs in Plecotus auritus and M. oxygnathus, and of PMVs in P. kuhlii. Conclusions: This study identified alpha and beta-CoVs in new bat species and in previously unsurveyed Italian regions. To our knowledge this represents the first and unique report of PMVs in Italy. The 23 new bat genetic sequences presented will expand the current molecular bat-borne virus databases. Considering the amount of novel bat-borne PMVs associated with the emergence of zoonotic infections in animals and humans in the last years, the definition of viral diversity within European bat species is needed. Performing surveillance studies within a specific geographic area can provide awareness of viral burden where bats roost in close proximity to spillover hosts, and form the basis for the appropriate control measures against potential threats for public health and optimal management of bats and their habitats