Estudo genético-clínico e citogenético de crianças autistas

Infantile autism is characterized by a typical behavior that may be caused by an organic disease or by an emotional disorder. The objective of the present genetic-clinical and cytogenetic study was to detect the presence of organic diseases, especially those of genetic etiology, that migth be related to the signs and symptons of autism presented by 17 boys who attended at the Ribeirão Preto Association for Autistic Children. We concluded that 14 individuals had no organic alterations that might be related to their clinical picture; one subject presented a clinical picture compatible with macrocephaly; one subject presented a clinical picture compatible with a new X-linked mental deficiency syndorme associated with macrossomy, macrocephaly and obesity, and one subject presented the Angelman Syndrome (AS). The study of Xq27.3 fragility was also normal in all cases, excluding the presence of Fragile X syndrome in all subjects. The specific molecular study for the detection of AS revealed the presence of biparental inheritance for the markers used. Since the clinical aspects of this patient was extremely suggestive, we conclude that he represented a case of AS with biparental inheritance.O autismo infantil é caracterizado pelo comportamento típico que pode ser causado por uma doença orgânica ou por um distúrbio emocional. Através de um estudo genético-clínico e citogenético, tivemos como objetivo detectar a presença de doenças orgânicas, principalmente de etiologia genética, que pudessem estar relacionadas com o quadro de autismo apresentado por dezessete meninos que freqüentavam a AMA de Ribeirão Preto. Concluímos que quatorze indivíduos não possuíam alterações orgânicas que pudessem estar relacionadas com o quadro clínico por eles apresentado; um indivíduo apresentou quadro clínico compatível com macrocefalia; um indivíduo apresentou quadro clínico compatível com uma nova síndrome de deficiência mental, ligada ao X, associada à macrossomia, macrocefalia e obesidade, e um indivíduo  presentou a Síndrome de Angelman (SA). O estudo citogenético mostrou-se normal para todos os indivíduos estudados, assim como a pesquisa de fragilidade Xq27.3, excluindo a todos da possibilidade de apresentarem a Síndrome do X-frágil. O estudo molecular, específico para a detecção da SA, revelou a presença, no paciente, de herança biparental para os marcadores utilizados; como a clínica desse paciente é extremamente sugestiva, concluímos estar frente a um caso de SA com herança biparental

Biochemical and genetic analysis of butyrylcholinesterase (BChE) in a family, due to prolonged neuromuscular blockade after the use of succinylcholine

Butyrylcholinesterase (BChE) is a plasma enzyme that catalyzes the hydrolysis of choline esters, including the muscle-relaxant succinylcholine and mivacurium. Patients who present sustained neuromuscular blockade after using succinylcholine usually carry BChE variants with reduced enzyme activity or an acquired BChE deficiency. We report here the molecular basis of the BCHE gene underlying the slow catabolism of succinylcholine in a patient who underwent endoscopic nasal surgery. We measured the enzyme activity of BChE and extracted genomic DNA in order to study the promoter region and all exons of the BCHE gene of the patient, her parents and siblings. PCR products were sequenced and compared with reference sequences from GenBank. We detected that the patient and one of her brothers have two homozygous mutations: nt1615 GCA > ACA (Ala539Thr), responsible for the K variant, and nt209 GAT > GGT (Asp70Gly), which produces the atypical variant A. Her parents and two of her brothers were found to be heterozygous for the AK allele, and another brother is homozygous for the normal allele. Sequence analysis of exon 1 including 5′UTR showed that the proband and her brother are homozygous for –116GG. The AK/AK genotype is considered the most frequent in hereditary hypocholinesterasemia (44%). This work demonstrates the importance of defining the phenotype and genotype of the BCHE gene in patients who are subjected to neuromuscular block by succinylcholine, because of the risk of prolonged neuromuscular paralysis

ProbFAST: Probabilistic Functional Analysis System Tool

<p>Abstract</p> <p>Background</p> <p>The post-genomic era has brought new challenges regarding the understanding of the organization and function of the human genome. Many of these challenges are centered on the meaning of differential gene regulation under distinct biological conditions and can be performed by analyzing the Multiple Differential Expression (MDE) of genes associated with normal and abnormal biological processes. Currently MDE analyses are limited to usual methods of differential expression initially designed for paired analysis.</p> <p>Results</p> <p>We proposed a web platform named ProbFAST for MDE analysis which uses Bayesian inference to identify key genes that are intuitively prioritized by means of probabilities. A simulated study revealed that our method gives a better performance when compared to other approaches and when applied to public expression data, we demonstrated its flexibility to obtain relevant genes biologically associated with normal and abnormal biological processes.</p> <p>Conclusions</p> <p>ProbFAST is a free accessible web-based application that enables MDE analysis on a global scale. It offers an efficient methodological approach for MDE analysis of a set of genes that are turned on and off related to functional information during the evolution of a tumor or tissue differentiation. ProbFAST server can be accessed at <url>http://gdm.fmrp.usp.br/probfast</url>.</p

Algas Marinhas do litoral da Ilha Graciosa

III Expedição Científica do Departamento de Biologia – Graciosa 1988.As algas dos Açores tem sido, do ponto de vista sistemático, objecto de interesse de alguns cientistas (Seubert, 1844; Drouet, 1866; Agardh, 1870; Godman, 1870; Trealese, 1897; Gain, 1914; Schmidt, 1930, 1931; Palminha, 1957; Larkurn, 1960; Pryor, 1967; Fralick et al., 1985; Casto & Viegas, 1987; Reine, 1988; Fralik & Hehre, no prelo. 0s registos existentes para Graciosa limitam-se, no entanto, a nove taxa. Este trabalho tem como objectivo contribuir para uma inventariação da flora algológica desta ilha e surge como ponta de partida para um conhecimento mais profundo da algologia e da ecologia marinha das ilhas dos Açore

Clinical profile and molecular characterization of Galactosemia in Brazil: identification of seven novel mutations

Abstract Background Classical Galactosemia (CG) is an inborn error of galactose metabolism caused by the deficiency of the galactose-1-phosphate uridyltransferase enzyme. It is transmitted as an autosomal recessive disease and is typically characterized by neonatal galactose intolerance, with complications ranging from neonatal jaundice and liver failure to late complications, such as motor and reproductive dysfunctions. Galactosemia is also heterogeneous from a molecular standpoint, with hundreds of different mutations described in the GALT gene, some of them specific to certain populations, reflecting consequence of founder effect. Methods This study reviews the main clinical findings and depicts the spectrum of mutations identified in 19 patients with CG, six with Duarte Galactosemia and one with type 2 Galactosemia in Brazil. Some individuals were diagnosed through expanded newborn screening test, which is not available routinely to all newborns. Results The main classical Galactosemia mutations reported to date were identified in this study, as well as the Duarte variant and seven novel mutations - c.2 T > C (p.M1T), c.97C > A (p.R33S), c.217C > T (p.P73S), c.328 + 1G > A (IVS3 + 1G > A), c.377 + 4A > C (IVS4 + 4A > C), c.287_289delACA (p.N97del) and c.506A > C (p.Q169P). This was expected, given the high miscegenation of the Brazilian population. Conclusions This study expands the mutation spectrum in GALT gene and reinforces the importance of early diagnosis and introduction of dietary treatment, what is possible with the introduction of Galactosemia in neonatal screening programs

1031-1034delTAAC (Leu125Stop): a novel familial <it>UBE3A</it> mutation causing Angelman syndrome in two siblings showing distinct phenotypes

<p>Abstract</p> <p>Background</p> <p>More than 50 mutations in the <it>UBE3A</it> gene (E6-AP ubiquitin protein ligase gene) have been found in Angelman syndrome patients with no deletion, no uniparental disomy, and no imprinting defect.</p> <p>Case Presentation</p> <p>We here describe a novel <it>UBE3A</it> frameshift mutation in two siblings who have inherited it from their asymptomatic mother. Despite carrying the same <it>UBE3A</it> mutation, the proband shows a more severe phenotype whereas his sister shows a milder phenotype presenting the typical AS features.</p> <p>Conclusions</p> <p>We hypothesized that the mutation Leu125Stop causes both severe and milder phenotypes. Potential mechanisms include: i) maybe the proband has an additional problem (genetic or environmental) besides the <it>UBE3A</it> mutation; ii) since the two siblings have different fathers, the <it>UBE3A</it> mutation is interacting with a different genetic variant in the proband that, by itself, does not cause problems but in combination with the <it>UBE3A</it> mutation causes the severe phenotype; iii) this <it>UBE3A</it> mutation alone can cause either typical AS or the severe clinical picture seen in the proband.</p