It is believed that a large number of people experience remaining symptoms after COVID-19, so-called post-COVID. The formal definition and diagnostic criteria of post-COVID have been a scientific controversy. So far, there is no reliable system for distinguishing the severity of post-COVID. This type of measurement would be helpful in future targeted therapies. Therefore, this thesis aims to evaluate the relationship between an individual’s functional status today and the symptoms present as well as identify relevant groups of post-COVID based on these 17 long-term symptoms of post-COVID. Further, to produce a model for which of these groups an individual belongs to. By using cluster analysis and ordinal logistic regression, Post-COVID Syndrome scores are produced. That is based upon both subjects who were hospitalised and those who were not, collected through a project called COMBAT post-covid. The individuals are then divided into groups based on these scores, and a prediction model is made using ordinal logistic regression and backward deletion. Three well-separated groups of post-COVID are found based on the produced scores. The prediction model indicates that the nine variables Sex, BMI, Smoking, Snuff, Heart disease, Lung disease, Diabetes, Chronic pain and Symptom severity at the onset seem important for predicting someone’s group. This study showed that the remaining symptoms affected an individual’s functional status, including self-reported working ability and general health.

Glaucoma is a heterogeneous group of diseases that is currently considered to be the leading cause of irreversible blindness worldwide. Of the identified risk factors, elevated intraocular pressure remains the only modifiable risk factor that can be targeted clinically. Ocular hypertension is often a result of dysregulation of aqueous humour fluid dynamics in the anterior eye segment. Aqueous humour drainage is regulated by structures located in the anterior chamber of the eye. In some circumstances dysregulation occurs due to developmental abnormalities of these structures. The malformation of structures in the anterior segment is thought to be due to a defect in the differentiation and/or migration of the periocular mesenchyme during development. Unique to vertebrates, the neural crest cell (NCC) population contributes to the periocular mesenchyme and is instrumental to the proper development of structures in the anterior segment. For many years our laboratory has examined the role of the Activating Protein-2 (AP-2) transcription factors that are expressed in the neural crest and vital during the development of the eye. The purpose of this research project is to investigate the role of AP-2β in the NCC population during the development of the anterior segment of the eye. Conditional deletion of AP-2β expression in the NCC population demonstrated that mutants have dysgenesis of structures in the anterior segment including defects of the corneal endothelium, corneal stroma, ciliary body and a closed iridocorneal angle. Loss of retinal ganglion cells and their axons was also observed, likely due to the disruption of aqueous outflow, suggesting the development of glaucoma. The data generated from this research project will be critical in elucidating the role of AP-2β in the genetic cascade dictating the development of the anterior eye segment in addition to providing scientific research with a novel model of glaucomatous optic neuropathy. / Thesis / Master of Science (MSc)

No description available.

No description available.

Thèse numérisée par la Direction des bibliothèques de l’Université de Montréal / While content selection has been intensively explored in the sentence extraction approach to automatic swnmarization, there is generally little work on the other process of content condensation. To understand this process of condensation, we propose a partial typology based on whether a linguistic unit is replaced, deleted, compressed into fewer essential units, or combined with another unit. Four important categories of condensation processes: generalization, deletion, compression, and aggregation, including their inverse processes, e.g. insertion, and expansion, which were occasionally observed, are proposed. To guide the usage of the same tenu for similar operations, we borrow definitions from linguistics. The type and function of the linguistic units involved are also discussed. We carried out an empirical analysis of 57 author-written abstracts of on-line journal articles in entomology, tracing each abstract sentence back to the plausible source sentences in the corresponding full text. Unlike other studies which focus on the resultant abstract, our study focuses on the processes leading to the production of abstract sentences from corresponding full-text sentences. We do not, however, propose an algorithm for abstracting, or account for all the conditions under which individual condensation operations may apply. While a range of substitutes were used in abstracting, about half of the stems of lexical units in our abstracts share the same stem as their source words, or are their derived forms. Only a small proportion of substitutes were synonyms, and the rest were (quasi-)synonyms, or imprecise equivalents. Authors tend to use less technical forms in abstracts possibly in anticipation of non-specialist abstract readers. Numerical expressions are rendered less precise although no less accurate: absolute numbers and decimals are rounded off, and percentages replaced by ratios or fractions. These observations are consistent with the "new" context of an abstract where only the gist of a document s content need be re-conveyed. Among the linguistic units commonly deleted are metadiscourse phrases, and segments of text (e.g. parenthetical texts, and apposed texts), which provide details and precision in the full text, but are out of place in an abstract. Redundancies inserted for various reasons, or units deemed to be implicit to the comprehension of targeted readers are also often removed. While deletion is an important sub-process of condensation, we observed some instances of adding experimental and other details to compact more information into abstract. The expansion or "unpacking" of compact linguistic units was also observed. The secondary role of inverse processes observed calls for a review of the meaning of condensation from "not giving as much detail or using fewer words" to include the adding of information in order to make a unit of text informatively compact. Among the linguistic units compressed are verbal complexes containing a support verb, or a catenative. Like semantically empty support verbs (e.g. X caused decreases in Y = X reduced Y), some catenatives too may be deleted without significant changes in meaning to the verbal complex (e.g. X was allowed to hatch E-e X hatched). Redundancy in meaning between an adjective and a noun in a noun phrase, e.g. functional role, may be removed, and the phrase compressed to just the stem of the adjective, i.e. function. While not frequently occurring in the corpus studied, the compression of such units may be described by rules, and hence, might be operationalized for automatic abstracting. Aggregation, the combining of units of text within or between sentences, is an important sub-process of condensation. Two-thirds of sentences in abstracts studied were written using multiple sentences, and more sentences were combined without than with the use of an explicit sign, such as a connective, a colon or a semi-colon. If research in summarization is to progress beyond sentence selection, then we must work towards: (a) a clear distinction between operations that are condensation processes, and those that are not; (b) bringing operationally similar processes together under the same designation, and (c) a greater understanding of sub-processes constitutiiig condensation. To this end, our provisional typology for condensation, the range of type of linguistic units involved and their functions sets the first step to advance research into content condensation. We have only just begun to identify the condensation sub-processes in operation during abstracting. The factors that are critical on the interplay of these processes still need to be investigated.

[pt] Esta dissertação aborda um fenômeno pouco estudado no Português Brasileiro (PB): o sluicing, fenômeno no qual o sintagma de tempo (TP) de uma estrutura encabeçada por um elemento –QU é elidido, deixando explícito apenas o elemento –QU. Merchant (2001) argumenta que o sluicing envolve movimento –QU e apagamento do TP, e que disso segue a generalização, segundo a qual uma língua permitirá encalhamento de preposição no sluicing se o permite em sentenças simples. Almeida & Yoshida (2007) argumentam que o PB falseia essa generalização por permitir encalhamento de preposição em sluicing, mas não em sentenças simples. Rodrigues et al. (2009), todavia, propõe que existem duas raízes para o sluicing no PB: sluicing regular e pseudosluicing, sendo que o encalhamento de preposição ocorreria apenas nessas estruturas. A presente dissertação investiga a proposta de Rodrigues et al. (2009), por meio de experimento de juízo de gramaticalidade e metodologia experimental, para verificar relações entre apagamento de preposição e tipo de estrutura. Os resultados corroboram a proposta de Rodrigues et al. (2009), e apontam para uma restrição de identidade de ordem semântica entre o constituinte elidido e seu antecedente. Nossa conclusão sugere que: os dados PB não falseiam a generalização de Merchant; identidade semântica é suficiente para licenciar processos de elisão. Esse fenômeno é investigado à luz de uma proposta de integração entre a teoria linguística de vertente gerativista e a psicolinguística, proposta que tem caracterizado as pesquisas desenvolvidas no Laboratório de Psicolinguística e Aquisição da Linguagem (LAPAL) da PUC-Rio. / [en] This dissertation discusses an understudied phenomenon in Brazilian Portuguese (BP): sluicing, a phenomenon in which the tense phrase (TP) of a structure headed by an interrogative pronoun (-QU) is elided, leaving only the explicit -QU. Merchant (2001) argues that sluicing involves –wh movement and deletion in the phonological form of TP, and proposes the following generalization: a language L will allow preposition stranding in sentences with sluicing iff L allows this stranding in simple sentences. Almeida and Yoshida (2007) argue that the Brazilian Portuguese distorts this generalization as it allows preposition stranding in sluicing, but not in simple sentences. In contrast, Rodrigues et al. (2009) proposes that there are two processes of sluicing in Brazilian Portuguese: regular sluicing and pseudosluicing, with preposition stranding occurring only in these structures. This dissertation investigates the proposal of Rodrigues et al. (2009), leading a grammaticality judgment experiment and using experimental methodology in order to verify deletion relations between preposition and type of structure. The results support the proposal of Rodrigues et al. (2009), and point to a semantic identity between the elided constituent and its antecedent. Our findings suggest that: the Brazilian Portuguese data does not distort Merchant s generalization; and, semantic identity is sufficient for licensing elision processes. This phenomenon is investigated in light of an integrated proposal between generative linguistic theory and psycholinguistics, a proposal that has characterized the research being developed at the Laboratory of Psycholinguistics and Language Acquisition (LAPAL) at PUC-Rio.

INTRODUÇÃO: Os defeitos cardíacos congênitos (DCC) são um grupo de anormalidades estruturais mais prevalentes ao nascimento e uma das principais causas de morbidade e mortalidade infantil. Os fatores genéticos são importantes na etiologia dos DCC. Estudos têm mostrado a contribuição da variação no número de cópias (CNV) na gênese das malformações cardíacas. A deleção 22q11.2 é a causa mais comum de microdeleção humana e está relacionada com defeito cardíaco (DCC) conotruncal. O MLPA (Multiplex Ligation-dependent Probe Amplification) é um método eficaz para detectar microdeleções/microduplicações em pacientes com DCC. OBJETIVO: Detectar a presença da variação no número de cópias gênicas em pacientes portadores de cardiopatia conotruncal pela técnica de MLPA e associar ao fenótipo do paciente. MÉTODOS: Foram avaliados 39 pacientes (23 do sexo masculino, 16 do sexo feminino) com idade entre 2 dias e 19 anos (mediana de 6 anos), todos com cardiopatia conotruncal, a maioria dos pacientes (56%) apresentavam tetralogia de Fallot. Avaliação clínica e laboratorial foi realizada em todos os pacientes. O cariótipo foi normal em todos pacientes. MLPA foi realizada com os kits P064, P036/P070 e P250. RESULTADOS: Foram detectadas CNVs em sete pacientes: deleção 22q11.2, duplicação 22q11.2, duplicação 15q11.2, duplicação 20p12.2, deleção 19p, duplicação 15q e duplicação 8p23.2 com duplicação 10p12.31. As cardiopatias encontradas nestes pacientes foram: dupla via de saída de ventrículo direito (2), coartação da aorta, tetralogia de Fallot (3) e transposição de grandes artérias. Os achados clínicos extracardíacos encontrados nestes pacientes foram dismorfismo facial, dente neonatal, atrofia e displasia cerebral, atresia duodenal, dificuldade de aprendizado, insuficiência velofaríngea, aplasia de timo, refluxo gastroesofágico, hérnia umbilical, asma, infecções de vias aéreas frequente, déficit de crescimento e somente três apresentavam retardo no desenvolvimento neuropsicomotor (dup 15q11.2, dup 15q, del 22q11.2). As características clínicas foram compatíveis com o relatado na literatura associado com a microdeleção/microduplicação encontrada. Nenhuma destas alterações foram herdadas de seus pais testados em seis casos. CONCLUSÃO: O uso do MLPA possibilitou a detecção de CNVs em pacientes com DCC. O diagnóstico precoce das CNVs em pacientes com DCC auxilia na prevenção de morbidade e diminuição da mortalidade nestes pacientes, contudo em um país com regiões com poucos recursos laboratoriais genéticos uma avaliação clínica minuciosa em todo paciente com DCC é imprescindível para direcionar qual melhor exame deve ser realizado / INTRODUCTION: Congenital heart defects (CHD) are a group of structural abnormalities most prevalent birth and a major cause of infant morbidity and mortality. Genetic factors are important in the etiology of CHD. Studies have shown the contribution of copy number variation (CNV) in the genesis of cardiac malformations. The deleletion 22q11.2 is the most common cause of human microdeletion and is related conotruncal cardiac defect (DCC). The MLPA (Multiplex Ligation-dependent Probe Amplification) is an effective method to detect microdeletions/micoduplications in patients with CHD. PURPOSE: Detect the presence of gene copies number variation in the patients with conotruncal heart defect by MLPA technique and associate the phenotype of the patient. METHODS: 39 patients (23 males, 16 females) aged 2 days old - 19 years old (median= 6 years old) with conotruncal cardiac defect were evaluated. Tetralogy of Fallot was more prevalent heart defect (56%). All patients were evaluated clinical and laboratory. Karyotypes were normal in all pacients. MLPA was performed with the P064, P036/P070 and P250 kits. RESULTS: CNVs were detected in seven patients: 22q11.2 deletion, 22q11.2 duplication, 15q11.2 duplication, 20p12.2 duplication, 19p deletion, 15q duplication and 8p23.2 duplication with 10p12.31 duplication. The congenital heart defect found in these patients were: double outlet right ventricle (2), coarctation of the aorta, tetralogy of Fallot (3) and transposition of the great arteries. Clinical findings in these patients were facial dysmorphism, neonatal tooth, brain atrophy and dysplasia, duodenal atresia, learning disabilities, velopharyngeal insufficiency, thymic aplasia, gastroesophageal reflux, umbilical hernia, asthma, frequent infections of the airways , failure to thrive, and only three had delayed psychomotor development (dup 15q 11.2, dup 15q, del 22q11.2) The clinical features were consistent with those reported in the literature associated with the microdeletion /microduplication found. None of these alterations were inherited from six parents tested. CONCLUSIONS: MLPA was effective to detect CNVs in patients with CHD. Early diagnosis of CNVs in patients with CHD assists in preventing morbidity and decreased mortality in these patients, however, in a country with regions with few genetic laboratory resources a thorough clinical evaluation in all patients with CHD is essential to direct which should be further analyzed performed

Os modelos logísticos trinomiais podem ser interpretados como uma extensão natural do modelo logístico binomial para situações em que a resposta admite apenas três resultados. Introduzimos inicialmente os modelos logísticos trinomiais e discutiremos em seguida alguns aspectos inferenciais, tais como estimação e testes. Medidas de qualidade do ajuste são também apresentadas. Contudo, o principal foco deste trabalho é a apresentação de métodos de diagnóstico. Mostramos que as técnicas usuais de diagnóstico desenvolvidas para o modelo logístico binomial podem ser adaptadas para o caso trinomial. O desenvolvimento de métodos diretos para o modelo logístico trinomial é mais complexo do ponto de vista computacional, embora seja sempre possível. Discutimos alguns desses métodos, dentre os quais, o desenvolvimento de resíduos, de métodos para detectar pontos de alavanca, métodos de deleção de pontos e influência local. Comparamos os métodos adaptados com alguns métodos diretos através de exemplos. / The trinomial logistic models can be interpreted as a natural extension of the traditional binomial logistic model to situations in which the response allows only three possible results. We firts introduce the trinomial logistic modles and then some inferential aspects, such as estimation and hypothesis testing are discussed. Good-of-fit measures are also given. However, the aim of this work is the presentation of some diagnostic procedures for trinomial logistic models. We show that methods developed for binomial logistic models can adapted straightforward for trinomial models. The developement of direct methods, even though possible, in general requires more complex calculation. Some of these direct methods, suchs as evaluation of residuals, measures of high leverage points, deletion methods and local influence are apresented. Coparisons between adapted and direct methods are made via examples with real data.

Objetivos: Investigar a ocorrência de queixa respiratória nos pacientes com sinais clínicos da Síndrome Velocardiofacial (SVCF) submetidos à cirurgia para a correção da Disfunção Velofaríngea (DVF), comparativamente àqueles com fissura isolada de palato sem sinais da SVCF, além de verificar se a condição respiratória pré-cirúrgica interfere na escolha do tratamento cirúrgico para correção da DVF. Material e Método: Estudo retrospectivo e prospectivo com 30 indivíduos de ambos os sexos, que realizaram procedimento cirúrgico para a correção da DVF (veloplastia intravelar ou retalho faríngeo), sendo 15 com sinais clínicos da SVCF (grupo estudo) e 15 com fissura isolada de palato sem sinais clínicos da SVCF, pareado por sexo e idade (grupo controle). Um levantamento de sintomas respiratórias foi realizado utilizando-se três questionários, um aplicado antes e após a cirurgia (Caouette-Laberge et al 1992) e dois aplicados apenas após a cirurgia (Petry et al 2008, Berlin, proposto por Netzer et al 1999). As comparações foram realizadas por meio do Teste Exato de Fisher, considerando-se nível de significância de 5%. Resultados: Sintomas como respiração oral e ronco estavam presentes nos períodos pré e pós-cirúrgico em ambos os grupos estudados, não sendo detectada diferença entre esses períodos quanto à presença desses sintomas, nos dois grupos. Diferença entre os grupos não foram constatadas em relação à presença de sonolência diurna excessiva, ronco, apneia, sono/fadiga, histórico de obesidade ou hipertensão arterial e risco potencial para SAOS. No grupo estudo houve semelhante distribuição entre a realização de veloplastia intravelar e retalho faríngeo, diferentemente do grupo controle em que prevaleceu a veloplastia intravelar, não havendo relação entre a frequência de sintomas respiratórios e o tipo de cirurgia, para ambos os grupos. Conclusão: Nos pacientes com sinais clínicos da SVCF, sintomas de respiração oral e ronco estão presentes antes e após a correção cirúrgica da DVF; não há diferença quanto aos sintomas respiratórios entre indivíduos com sinais clínicos da SVCF e indivíduos com fissura isolada de palato sem sinais da SVCF; a condição respiratória antes da cirurgia não interferiu na escolha do tipo de procedimento cirúrgico para correção da DVF. / Objectives: To investigate the occurrence of respiratory complaint in individuals with clinical signs of Velocardiofacial Syndrome (VCFS) submitted to surgery for correction of Velopharyngeal Dysfunction (VPD), compared to individuals without signs of VCFS, and analyzed if the preoperative respiratory condition interferes with surgical treatment planning for correction of VPD. Material and method: Retrospective and prospective study of 30 individuals of both genders, who were submitted to surgery for correction of VPD (intravelar veloplasty or pharyngeal flap), being 15 with clinical signs of VCFS (study group) and 15 with isolated cleft palate without clinical signs of VCFS, matched for gender and age (control group). A survey of respiratory complaints was performed using three questionnaires, one applied before and after surgery (Caouette-Laberge et al 1992) and two applied only after surgery (Petry et al 2008, Berlin, proposed by Netzer et al 1999). Comparisons were performed by the exact Fisher test, at a significance level of 5%. Results: Symptoms as mouth breathing and snoring were present in pre- and postoperative periods in both groups, without difference between periods concerning the presence of these symptoms, in the two groups. No differences were observed between groups as to the presence of excessive somnolence during the day, snoring, apnea, sleep/fatigue, history of obesity or arterial hypertension and potential risk to OSA. The study group presented similar distribution of intravelar veloplasty and pharyngeal flap, different from the control group that presented predominance of intravelar veloplasty, without relationship between the frequency of respiratory symptons and type of surgery, for both groups. Conclusion: In patients with clinical signs of VCFS, complaints of mouth breathing and snoring are present before and after surgical correction of VPD; there is no difference in the complaints of respiratory symptoms between individuals with clinical signs of VCFS and individuals with isolated cleft palate without signs of VCFS; the respiratory condition before surgery did not interfere with selection of the type of surgical procedure for correction of VPD.

A incidência dos tumores adrenocorticais na região sul do Brasil é 10-15 vezes maior que a incidência mundial. Mutações no gene supressor tumoral p53, localizado na região 17p13.1 têm sido identificadas em diversos tumores humanos. Uma distinta mutação germinativa, Arg337His, localizada no domínio de tetramerização da proteína supressora tumoral P53 foi identificada em 35 de 36 crianças da região sul do Brasil. No presente trabalho, investigamos a presença da mutação Arg337His em 71 pacientes não relacionados, 41 adultos e 30 crianças, portadores de tumores adrenocorticais benignos e malignos. Adicionalmente, análise de perda de heterozigose do locus p53, mapa de deleção do cromossomo 17 e instabilidade cromossômica foram estudados em DNA genômico destes pacientes. Nenhum dos pacientes estudados apresentava histórico familial compatível com a síndrome de Li-Fraumeni. Sequenciamento automático permitiu a identificação da mutação Arg337His, em DNA extraído a partir de sangue periférico e/ou tecido tumoral, em 29 (24 crianças e 5 adultos) dos 71 pacientes. Nas 10 famílias em que foi possível analisar o DNA genômico de ambos os pais verificamos que a mutação Arg337His tem caráter hereditário. Por outro lado, esta mutação não foi encontrada em DNA de 160 indivíduos do grupo controle, não relacionados, analisados por sequenciamento automático e/ou digestão enzimática. A análise pareada de DNA gênomico de sangue periférico e de tecido tumoral revelou perda de heterozigose para o locus p53 em 18 de 21 (86%) pacientes portadores da mutação Arg337His. Não observamos correlação entre a presença desta mutação e o comportamento maligno dos tumores. O estudo de dois marcadores polimórficos intragênicos do p53, pelo programa de análise de tamanho de fragmento GeneScan, evidenciou um mesmo haplótipo associado à mutação Arg337His em 91% dos pacientes com tumores adrenocorticais, configurando uma origem comum para esta mutação. O estudo de 6 marcadores polimórficos ao longo do cromossomo 17 (D17S926, VNTRP53, D17S1856, D17S942, D17S1351 e D17S928) em DNA genômico pareado de 29 pacientes demonstrou uma freqüência elevada (81%) de perda do cromossomo 17 em associação à mutação Arg337His. Não observamos correlação entre a perda do cromossomo 17 e a agressividade tumoral nestes pacientes. Instabilidade cromossômica envolvendo os cromossomos 2, 9 e 11 nos 17 pacientes que perderam o cromossomo 17 foi identificada em 47%, 47% e 71%, respectivamente. Perda dos cromossomos 2 e 11 foi evidenciada em tumores benignos e malignos. A perda do cromossomo 9 foi evidenciada exclusivamente nos tumores malignos, assim como a perda concomitante de 3 ou mais cromossomos. Em conclusão, confirmamos uma freqüência elevada da mutação Arg337His em crianças brasileiras com tumores adrenocorticais benignos e malignos. Esta mutação também foi encontrada no grupo de adultos, embora em menor freqüência. Não houve correlação entre sua presença e o comportamento maligno dos tumores adrenocorticais. Efeito fundador para a mutação Arg337His e inativação bialélica do p53, caracterizada pela presença da mutação Arg337His e a perda do cromossomo 17 foram demonstradas na maioria dos casos analisados. Finalmente, a instabilidade cromossômica envolvendo três ou mais cromossomos contribuiu para o diagnóstico de carcinoma adrenocortical / The incidence of adrenocortical tumors in the South region of Brazil is 10 to 15 times higher than the worldwide one. Mutations in the tumor suppressor p53 gene, located in chromosome 17p13.1, have been described in different human tumors. A germline mutation, Arg337His, in the tetramerization domain of the tumor suppressor P53 was identified in 35 of 36 children from the South region of Brazil. In the present study we have searched for Arg337His mutation in genomic DNA of 71 non-related patients, 41 adults and 30 children, with benign or malignant adrenocortical tumors. Additionally, we also analyzed the loss of heterozigosity of p53 locus, deletion mapping of chromosome 17 and chromosome instability, in genomic DNA of these patients. None of the patients had a familial history of Li-Fraumeni syndrome. Automatic sequencing identified the Arg337His mutation in genomic DNA from peripheral leukocytes and/or tumor tissues in 29 (24 children and 5 adults) of these 71 patients. In 10 families in which the study of both parent\'s DNA was possible, the Arg337His mutation was inherited from one of the parents. Sequencing analysis and/or enzymatic restriction showed that this mutation was not present in DNA of 160 non-related control subjects. Paired analysis of genomic DNA of peripheral leukocytes and tumor tissue revealed loss of heterozigosity of p53 locus in 18/21 (86%) patients with Arg337His mutation. There was no correlation between the presence of this mutation and the malignant behavior of these tumors. The study of two intragenic polymorphic markers of p53 through GeneScan software showed the association of the same haplotype with the Arg337His mutation in 91% of patients with adrenocortical tumors, indicating a common origin of this mutation. The study of 6 polymorphic markers along chromosome 17 (D17S926, VNTRP53, D17S1856, D17S942, D17S1351, D17S928) in paired genomic DNA of 29 patients showed an increased frequency (81%) of chromosome 17 loss in association with the presence of the Arg337His mutation. We did not observe any correlation between the loss of chromosome 17 and aggressive tumor behavior in these patients. In the 17 patients who lost chromosome 17, chromosome instability of chromosomes 2, 9 and 11 was identified in 47%, 47% e 71%, respectively. Loss of chromosomes 2 and 11 was observed in benign and malignant tumors, whereas the loss of chromosome 9 was observed exclusively on malignant tumors. Similarly, the concomitant loss of 3 or more chromosomes was only observed in malignant tumors. In conclusion we confirmed an increased frequency of Arg337His mutation in Brazilian children with benign or malignant adrenocortical tumors. This mutation was also found in the adult group, although at a lower frequency. There was no correlation between the presence of the mutation and the malignant behavior of adrenocortical tumor. We demonstrated a founder effect for this mutation and also a biallelic inactivation of p53 characterized by the presence of the Arg337His mutation and the loss of chromosome 17 in most of the cases studied. Finally, chromosome instability involving 3 or more chromosomes contributed for the diagnosis of adrenocortical carcinoma in these