Expanding the clinical phenotype of individuals with a 3-bp in-frame deletion of the NF1 gene (c.2970_2972del): an update of genotype–phenotype correlation

Purpose: Neurofibromatosis type 1 (NF1) is characterized by a highly variable clinical presentation, but almost all NF1-affected adults present with cutaneous and/or subcutaneous neurofibromas. Exceptions are individuals heterozygous for the NF1 in-frame deletion, c.2970_2972del (p.Met992del), associated with a mild phenotype without any externally visible tumors. Methods: A total of 135 individuals from 103 unrelated families, all carrying the constitutional NF1 p.Met992del pathogenic variant and clinically assessed using the same standardized phenotypic checklist form, were included in this study. Results: None of the individuals had externally visible plexiform or histopathologically confirmed cutaneous or subcutaneous neurofibromas. We did not identify any complications, such as symptomatic optic pathway gliomas (OPGs) or symptomatic spinal neurofibromas; however, 4.8% of individuals had nonoptic brain tumors, mostly low-grade and asymptomatic, and 38.8% had cognitive impairment/learning disabilities. In an individual with the NF1 constitutional c.2970_2972del and three astrocytomas, we provided proof that all were NF1-associated tumors given loss of heterozygosity at three intragenic NF1 microsatellite markers and c.2970_297

Suplementação de bovinos em pastagem de Coastcross (Cynodon dactylon (L.) Pers) no verão Cattle supplementation on coastcross pasture (Cynodon dactylon (L.) Pers) during the summer

O experimento foi realizado no município de Luiziana, noroeste do Estado do Paraná, no período de outubro de 2000 a fevereiro de 2001. Foram utilizados 32 novilhos inteiros, com 13 meses de idade e peso inicial médio de 325 kg, pertencentes a dois grupos genéticos distintos, sendo 20 ½ Red Angus ½ Nelore e 12 ½ Marchigiana ½ Nelore. Avaliou-se o desempenho destes animais, em quatro piquetes de Coastcross (Cynodon dactylon (L.) Pers), perfazendo um total de 5,05 ha e diferentes níveis de suplementação energética (na base de 0; 0,2; 0,4; e 0,6% do peso vivo) com casca de soja. Foram realizadas estimativas da disponibilidade e da qualidade da forragem. Após 112 dias de experimento, observaram-se elevados ganhos de peso para todos os tratamentos (acima de 0,850 kg/dia).<br>This trial was carried out in Luiziana, northwest of Paraná, from November 2000 to February 2001. Twenty-four animals with 325 kg of initial body weight and 13 months of age, from two different genetic groups, ½ Red Angus ½ Nellore (20) and ½ Marchigiana ½ Nellore (12) were used. Animal performance was evaluated, under grazing conditions on coastcross (Cynodon dactylon (L.) Pers) and four levels of soybean hulls: 0, 0.2, 0.4, and 0.6% of body weight. Pasture production and quality were also evaluated. The experimental area consisted of four paddocks of Coastcross, with 5.05 ha of total area. After 112 days of experimental period, all treatments showed high gains per animal (above 0.850 kg/day)

Suplementação de bovinos em pastagens de Coastcross (Cynodon dactylon (L.) Pers) no inverno Cattle supplementation on Coastcross pasture (Cynodon dactylon (L.) Pers) during the winter

O experimento foi realizado no município de Luiziana, noroeste do Estado do Paraná, no período de junho a outubro de 2000. Foram utilizados 24 novilhos inteiros, com nove meses de idade e peso inicial médio de 223 kg, pertencentes a dois grupos genéticos distintos, sendo 15 ½ Red Angus ½ Nelore e nove ½ Marchigiana ½ Nelore. Avaliou-se o desempenho dos animais submetidos a três formas de suplementação e a qualidade e produtividade da forragem. A área experimental foi constituída por quatro piquetes, sendo três de Coastcross (Cynodon dactylon (L.) Pers), com área total de 7,35 ha e um de Aveia (Avena strigosa Schreb), consorciada com Azevém (Lolium multiflorum Lam), totalizando 2 ha. Os novilhos permaneceram em pastagens de Coastcross e foram submetidos a três tratamentos: pastejo em Aveia + Azevém (AA) por quatro horas diárias; suplemento (S) a 1,2% do peso vivo; suplemento + lasalocida (SL) a 1,2% do peso vivo. Estimativas da biomassa e da qualidade das forrageiras foram realizadas. Decorridos 112 dias experimentais, S e SL não apresentaram diferença para ganho médio diário (GMD = 1,063 kg e 1,026 kg, respectivamente), mas foram superiores a AA (0,856 kg). Concluiu-se que a adição de lasalocida ao suplemento não produziu diferença no desempenho dos animais. Estes resultados comprovam que animais mantidos em pastagem de Coastcross, com quatro horas de pastejo em pastagem anual de inverno ou com suplementação (1,2% do peso vivo), independentemente da adição de ionóforo, apresentaram elevados ganhos na época crítica do ano.<br>This trial was carried out in Luiziana, Northwest of Paraná, from June to October 2000. Twenty-four animals with 223 kg of initial body weight and nine months old, from two different genetic groups, ½ Red Angus ½ Nellore (15) and ½ Marchigiana ½ Nellore (9), were used. Animal performance was evaluated, under grazing conditions of Coastcross (Cynodon dactylon (L.) Pers) and three types of supplementation: grazing Oat + Ryegrass pasture (OR) for four hours/day; 1.2% of body weight (BW) supplement (S); 1.2% of BW supplement + lasalocid (SL). The experimental area consisted of four padocks: three of Coastcross, with 7.35 ha of total area; and one of Oat (Avena strigosa Schreb) and Ryegrass (Lolium multiflorum Lam), with two ha. Pasture accumulation and quality were evaluated. After 112 days of experimental period, average daily gain did not show any difference between S and SL (1.063 kg and 1.026 kg, respectively), but both were superior than OR (0.856 kg). Lasalocid addition to supplement did not improve animal performance. These results show that even during the dry period, supplementation (1.2% of BW), with or without lasalocid, or winter pasture, can result in high liveweight

The Fourth International Symposium on Genetic Disorders of the Ras/MAPK pathway

The RASopathies are a group of disorders due to variations of genes associated with the Ras/MAPK pathway. Some of the RASopathies include neurofibromatosis type 1 (NF1), Noonan syndrome, Noonan syndrome with multiple lentigines, cardiofaciocutaneous (CFC) syndrome, Costello syndrome, Legius syndrome, and capillary malformation-arteriovenous malformation (CM-AVM) syndrome. In combination, the RASopathies are a frequent group of genetic disorders. This report summarizes the proceedings of the 4th International Symposium on Genetic Disorders of the Ras/MAPK pathway and highlights gaps in the field