Array-CGH analysis in patients with intellectual disability and/or congenital malformations in Brazil.

In several patients, intellectual disability and/or congenital malformation may be attributed to chromosomal changes. In this study, we conducted an array-CGH test of 200 patients from the Northeast of Brazil with intellectual disability and/or congenital malformation. Blood samples were collected from the proband and from their parents when possible. DNA was extracted and investigated using the array-CGH test. Findings were evaluated for the pathogenicity in databases of benign and pathogenic changes (ISCA, UCSC, DGV, and DECIPHER). Forty-seven copy number variations (CNVs) were identified in 43/200 (21.5%) patients, including 25/98 (25.5%) in males and 22/102 (21.57%) in females. We considered 33 of these to be clinically significant, reaching a diagnosis rate of 16.5%. The sizes of the CNVs varied from 102 kb to 24 Mb in deletions and from 115 kb to 140 Mb in duplications. In 10/47 (21.3%) patients, the rearrangement involved a sex chromosome. Thirty-nine patients had one chromosomal aberration, while 2 concomitant abnormalities were detected in 4 patients. Ten of 47 CNVs (21.3%) were > 5Mb in size. Fifteen patients had CNVs related to known syndromes. This research highlights the contribution of submicroscopic chromosomal changes to the etiology of intellectual disability and/or congenital malformation, particularly the implication of chromosomal abnormalities detected using an array-CGH test, with a high rate of 16.5%. Thus, our results support the use of array-CGH replacing standard karyotype as the first-tier cytogenetic diagnostic test for patients with multiple congenital anomalies and/or intellectual disability.

Hepatocellular carcinoma and estrogen receptors: Polymorphisms and isoforms relations and implications.

Hepatocellular carcinoma (HCC) is the most common primary tumor of liver and its incidence continues to increase worldwide. HCC is a disease with multifactorial causes and genetic variability has been discussed as a risk factor for its development. Liver is a hormone-sensitive organ and therefore is influenced by gonadal hormones, such as estrogen. Estrogen is known to participate in various biological functions, but its role in development of HCC, on the other hand, is controversial and presents evidence suggesting a role as both a carcinogen and protective effect in liver. Estrogen way of action is mediated by estrogen receptor alpha (ERα) and estrogen receptor beta (ERß), that belong to a family of nuclear receptors that may regulate the expression of many genes. The ER subtypes exert a variety of roles in many stages of liver disease and may play a part in the process of signal transduction, according to some studies. However, the many functions of ER subtypes in hepatic diseases, in special of the ERß, are yet to be clarified. The genetic modifications related to HCC are not yet fully clarified and accumulation of multiple genetic alterations appears to have an important role in carcinogenesis of HCC. The presence of some certain single nucleotide polymorphism (SNP) may have a functional repercussion related to final product of a gene, which can be measured and may participate in some alterations related to a pathological condition. Our hypothesis is based on the fact that liver tissue express ER and its different variants exert multiple functions in various stages of liver disease and participate in an extremely complicated signal transduction process, therefore we believe that the presence of one or more SNPs of ESR1 and ESR2 genes may be related with the increase of risk in developing and the severity of HCC, as well as in the response to different treatments. The confirmation of our hypothesis by scientific studies may provide knowledge of markers that act as prognostic factors of this disease, as well as enabling alternatives to development of anti tumoral therapies.

Association between subjective evaluation and physical parameters for radiographic images optimization.

PURPOSE: The purpose of this study was to develop a methodology to optimize computed radiographic techniques to image the skull, chest, and pelvis of a standard patient. METHODS: Optimization was performed by varying exposure levels with different tube voltages to generate images of an anthropomorphic phantom. Image quality was evaluated using visual grading analysis and measuring objective parameters such as the effective detective quantum efficiency and the contrast-to-noise ratio. Objective and subjective evaluations were compared to obtain an optimized technique for each anatomic region. RESULTS: Gold standard techniques provided a significant reduction in X-ray doses compared to the techniques used in our radiology service, without compromising diagnostic accuracy. They were chosen as follows 102 kVp/1.6 mAs for skull; 81 kVp/4.5 mAs for pelvis and 90 kVp/3.2 mAs for chest. CONCLUSION: There is a range of acceptable techniques that produce adequate images for diagnosis in computed radiography systems. This aspect allows the optimization process to be focused on the patient dose without compromising diagnostic capabilities. This process should be performed through association of quantitative and qualitative parameters, such as effective detective quantum efficiency, contrast-to-noise ratio, and visual grading analysis.

Quality and dose optimization in hand computed radiography.

The objective of the present study was to optimize a radiographic technique for hand examinations using a computed radiography (CR) system and demonstrate the potential for dose reductions compared with clinically established technique. An exposure index was generated from the optimized technique to guide operators when imaging hands. Homogeneous and anthropomorphic phantoms that simulated a patient's hand were imaged using a CR system at various tube voltages and current settings (40-55 kVp, 1.25-2.8 mAs), including those used in clinical routines (50 kVp, 2.0 mAs) to obtain an optimized chart. The homogeneous phantom was used to assess objective parameters that are associated with image quality, including the signal difference-to-noise ratio (SdNR), which is used to define a figure of merit (FOM) in the optimization process. The anthropomorphic phantom was used to subjectively evaluate image quality using Visual Grading Analysis (VGA) that was performed by three experienced radiologists. The technique that had the best VGA score and highest FOM was considered the gold standard (GS) in the present study. Image quality, dose and the exposure index that are currently used in the clinical routine for hand examinations in our institution were compared with the GS technique. The effective dose reduction was 67.0%. Good image quality was obtained for both techniques, although the exposure indices were 1.60 and 2.39 for the GS and clinical routine, respectively.

Alternaria infectoria brain abscess in a child with chronic granulomatous disease.

In the present report, we describe the first case of a phaeohyphomycotic brain abscess in a 5-year-old boy with chronic granulomatous disease (CGD) admitted to hospital with seizures. A computed tomography (CT) scan revealed a cerebral abscess and the microbiology study showed a dark, melanin-pigmented fungus, exhibiting only sterile hyphae. This fungus was identified by the amplification and sequencing of the 5.8S RNA gene and of the adjacent internal transcriber spacer domains, ITS1 and ITS2, as Alternaria infectoria. Due to the impossibility of a surgical excision, and although several therapeutic strategies were attempted, the patient died. Limitations in the routine identification procedures and therapeutic options of this emerging opportunistic agent are highlighted in this report.

Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST).

Sclerosteosis is a progressive sclerosing bone dysplasia with an autosomal recessive mode of inheritance. Radiologically, it is characterized by a generalized hyperostosis and sclerosis leading to a markedly thickened and sclerotic skull, with mandible, ribs, clavicles and all long bones also being affected. Due to narrowing of the foramina of the cranial nerves, facial nerve palsy, hearing loss and atrophy of the optic nerves can occur. Sclerosteosis is clinically and radiologically very similar to van Buchem disease, mainly differentiated by hand malformations and a large stature in sclerosteosis patients. By linkage analysis in one extended van Buchem family and two consanguineous sclerosteosis families we previously mapped both disease genes to the same chromosomal 17q12-q21 region, supporting the hypothesis that both conditions are caused by mutations in the same gene. After reducing the disease critical region to approximately 1 Mb, we used the positional cloning strategy to identify the SOST gene, which is mutated in sclerosteosis patients. This new gene encodes a protein with a signal peptide for secretion and a cysteine-knot motif. Two nonsense mutations and one splice site mutation were identified in sclerosteosis patients, but no mutations were found in a fourth sclerosteosis patient nor in the patients from the van Buchem family. As the three disease-causing mutations lead to loss of function of the SOST protein resulting in the formation of massive amounts of normal bone throughout life, the physiological role of SOST is most likely the suppression of bone formation. Therefore, this gene might become an important tool in the development of therapeutic strategies for osteoporosis.

[Idiopathic pulmonary hemosiderosis: case report] / Hemossiderose pulmonar idiopática: relato de caso.

OBJECTIVE: To alert pediatricians about the possibillity of childhood Idiopathic Pulmonary Hemosiderosis, in cases of anemia associated with chronic lung disease. METHODS: This article documents a case of Idiopathic Pulmonary Hemosiderosis in a 6 year-old child, with histopathological documentation, and reviews it against published literature. RESULTS: A 6 year-old child with history of anemia and lung disease characterized by wheezing, recurrent pneumonia and digital clubbing was admitted to the hospital for investigation, where he suffered sudden respiratory failure and hemoptysis.He was submitted to a lung biopsy which showed a histopathological diagnosis compatible with pulmonary hemosiderosis. Therapy with high doses of corticosteroids was initiated with a good early response. After two and a half months of therapy he had a new bleeding episode, culminating in death. CONCLUSIONS: Idiopathic Pulmonary Hemosiderosis should be included as a possible diagnosis of children with anemia and chronic lung disease. This case is a good example.

Autosomal recessive malformation syndrome with minor manifestation in the heterozygotes: a preliminary report of a possible new syndrome.

We describe 3 patients with a new malformation syndrome in 2 sibships in a large kindred from Bahia, Brazil. The parents in both sibships are consanguineous. The syndrome is characterized by malformations of the face, ears, hands and feet, plus mixed deafness and pseudopapilledema. Fifty-four relatives were examined clinically and scored by the number of anomalies. A control sample of 54 individuals was equally examined. The distribution of the number of anomalies per individual (score) is bimodal in the relatives of the patients but unimodal in the control individuals. Detection of heterozygotes was based on the score distribution.

Short stature in a patient with cystic fibrosis caused by a 6.7-kb human growth hormone gene deletion.

A recent longitudinal study in children with cystic fibrosis (CF) challenged the common idea that CF is causing short stature. The data, however, showed clearly that short stature cannot be explained by CF alone after the first year of life. We report on a girl suffering from CF and short stature in whom DNA analysis using polymerase chain reaction and Southern blot techniques of the human growth hormone (hGH) gene cluster revealed a 6.7-kb gene deletion encompassing the hGH-1 gene. Anti-hGH antibodies of polyclonal origin developed, leading to a growth arrest after only 2 months of hGH replacement. In addition, a family study was performed, and the haplotypes of the CF gene and hGH gene cluster were analyzed.

[Evaluation of cardiac manifestations in hypothyroidism: documentation of reversibility]. / Avaliação das manifestações cardíacas no hipotireoidismo: documentação da reversibilidade.

PURPOSE: To detect the cardiac manifestations due to the state of hypothyroidism and reversibility after euthyroidism. PATIENTS AND METHODS: Thirteen patients with documented primary hypothyroidism were evaluated through the echocardiography and other noninvasive techniques. A new evaluation was performed six months after thyroid hormone therapy. RESULTS: Most of the changes were reversed after the patients became euthyroid. The main finding was the echocardiographic measurement of the velocity of circumferential fiber shortening that showed a significant positive linear correlation with serum thyroid hormones. CONCLUSION: These data demonstrate the existence of a hypothyroid cardiomyopathy.

An autosomal recessive ectodermal dysplasia syndrome of hypotrichosis, onychodysplasia, hyperkeratosis, kyphoscoliosis, catartact, and other manifestations.

We describe a 20-year-old woman with generalized trichodysplasia, dry skin with scaling, hyperchromic spots on limbs, hyperkeratosis (particularly intense on soles), dermatoglyphic abnormalities, onychodysplasia, shortness of stature, kyphoscoliosis, unusual facial appearance, minor malformations of limbs, bilateral nuclear cataract, narrow palpebral fissures, entropion, trichiasis, etc. The condition is probably due to an autosomal recessive gene. The patient is the only affected member in a sibship of four whose parents are second cousins.

Alguns aspectos da sindrome de Mc Cune-Albright. Relato de um caso e revisao da literatura. / Mc Cune-Albright Syndrome. Report of a case and review of the literature

Os autores relatam um caso de uma paciente portadora da sindrome de Mc Cune-Albright, tecem comentarios sobre os aspectos geneticos endocrinos, radiologicos e anatomopatologicos dessa sindrome. Sao discutidas as diversas hipoteses da patogenese das manifestacoes apresentadas, concluindo-se que ate o presente nao existe hipotese capaz de explicar todas as alteracoes. Cuidadosa revisao da literatura sobre o assunto e tambem apresentada

Incidencia de malignidade nas tiroidopatias em Hospital Geral. / The incidence of malignancy in thyroid diseases in a General Hospital

Os autores fazem uma avaliacao em termos de incidencia e mortalidade de neoplasias da tiroide em um Hospital Geral e comparam seus achados com os da literatura. As tiroidopatias contribuiram com 2,5% das intervencoes cirurgicas com incidencia de 11,1% de casos de carcinoma. O cancer da tiroide foi causa mortis em 6 (0,14%) das 4.222 necropsias

Distribution of abnormal hemoglobins and glucose-6-phosphate dehydrogenase variants in 1200 school children of Bahia, Brazil.

School children from Bahia, Brazil were studied for hemoglobin and glucose-6-phosphate dehydrogenase electrophoretic variants. Eighty-nine heterozygotes Hb AS and 41 Hb AC were identified out of 1200 children. In a subsample of 369 male children there were 38 Gd A-, 38 Gd A, and six Gd Med. An example of Gd MG was identified and evidence is added to the suggestion that this allele is not rare in Brazil.