Abstract Admixed populations have not been examined in detail in cancer genetic studies. Here, we inferred the local ancestry of cancer-associated single nucleotide polymorphisms (SNPs) and haplotypes of a highly admixed Brazilian population. SNP array was used to genotype 73 unrelated individuals aged 80-102 years. Local ancestry inference was performed by merging genotyped regions with phase three data from the 1000 Genomes Project Consortium using RFmix. The average ancestry tract length was 9.12-81.71 megabases. Strong linkage disequilibrium was detected in 48 haplotypes containing 35 SNPs in 10 cancer driver genes. All together, 19 risk and eight protective alleles were identified in 23 out of 48 haplotypes. Homozygous individuals were mainly of European ancestry, whereas heterozygotes had at least one Native American and one African ancestry tract. Native-American ancestry for homozygous individuals with risk alleles for HNF1B, CDH1, and BRCA1 was inferred for the first time. Results indicated that analysis of SNP polymorphism in the present admixed population has a high potential to identify new ancestry-associated alleles and haplotypes that modify cancer susceptibility differentially in distinct human populations. Future case-control studies with populations with a complex history of admixture could help elucidate ancestry-associated biological differences in cancer incidence and therapeutic outcomes.

Abstract COVID-19 comprises clinical outcomes of SARS-CoV-2 infection and is highly heterogeneous, ranging from asymptomatic individuals to deceased young adults without comorbidities. There is growing evidence that host genetics play an important role in COVID-19 severity, including inborn errors of immunity, age-related inflammation and immunosenescence. Here we present a brief review on the known order of events from infection to severe system-wide disturbance due to COVID-19 and summarize potential candidate genes and pathways. Finally, we propose a strategy of subject’s ascertainment based on phenotypic extremes to take part in genomic studies and elucidate intrinsic risk factors involved in COVID-19 severe outcomes.

RESUMO Objetivo A escassez de pulmões viáveis ainda é um grande obstáculo para o transplante. As vítimas de trauma, que constituem potenciais doadores de pulmão, comumente apresentam choque hipovolêmico que acarreta inflamação e deterioração pulmonar e rejeição após o transplante. Buscando melhorar o enxerto pulmonar, testaram-se novas abordagens ao tratamento do doador. Este estudo foca o tratamento com células-tronco mesenquimais (CTMs) ou fatores solúveis produzidos pelas CTMs (FS-CTMs), usando um modelo com ratos para doadores de pulmão após choque hemorrágico. Métodos Quarenta e oito ratos foram divididos em quatro grupos: Controle (n=12), animais sem indução de choque hipovolêmico; Choque (n=12), animais submetidos a choque hipovolêmico (pressão arterial média de 40 mmHg); CTM (n=12), animais submetidos a choque hipovolêmico e tratados com CTMs; e FS (n=12), animais submetidos a choque hipovolêmico e tratados com FS-CTMs. Os animais foram submetidos a um procedimento de choque hipovolêmico (40 mmHg) com 50 minutos de duração. Os animais tratados foram monitorados por 115 minutos. Realizamos análise histopatológica do tecido pulmonar e quantificação dos marcadores inflamatórios (TNF-α, IL-1β, IL-6, IL-10, iCAM e vCAM) no tecido pulmonar e leucócitos no sangue periférico (LSPs). Resultados O choque hemorrágico resultou em taxas mais altas de LSPs e infiltrado de neutrófilos nos pulmões. Os animais do grupo FS apresentaram menor densidade de neutrófilos em comparação com os animais dos grupos Choque e CTM (p<0,001). Não foram observadas diferenças entre os grupos quanto aos níveis de citocinas no tecido pulmonar. Conclusão Os pulmões dos ratos submetidos a choque hemorrágico e tratados com FS-CTM apresentaram inflamação reduzida indicada por uma diminuição do infiltrado de neutrófilos nos pulmões.

ABSTRACT Objective The shortage of viable lungs is still a major obstacle for transplantation. Trauma victims who represent potential lung donors commonly present hypovolemic shock leading to pulmonary inflammation and deterioration and rejection after transplantation. Seeking to improve lung graft, new approaches to donor treatment have been tested. This study focuses on treatment with mesenchymal stem cells (MSCs) or soluble factors produced by MSCs (FS-MSC) using a rat model for lung donors after hemorrhagic shock. Methods Forty-eight rats were divided into four groups: Sham (n=12), animals without induction of hypovolemic shock; Shock (n=12), animals submitted to hypovolemic shock (mean arterial pressure 40 mmHg); MSC (n=12), animals submitted to hypovolemic shock and treated with MSCs, and FS (n=12), animals submitted to hypovolemic shock and treated with FS-MSC. The animals were subjected to a 50-minute hypovolemic shock (40 mmHg) procedure. The treated animals were monitored for 115 minutes. We performed histopathology of lung tissue and quantification of inflammatory markers (TNF-α, IL-1β, IL-6, IL-10, iCAM and vCAM) in lung tissue and peripheral blood leukocytes (PBLs). Results Hemorrhagic shock resulted in higher PBLs and neutrophil infiltrate in the lungs. FS animals had lower neutrophil density comparing with Shock and MSC animals (p<0.001). No differences in the cytokine levels in lung tissue were observed between the groups. Conclusions The lungs of rats submitted to hemorrhagic shock and treated with FS-MSC showed reduced inflammation indicated in a decrease in lung neutrophil infiltrate.

Resumo Objetivo: Analisar, quantitativamente, o volume cerebral de idosos em uma amostra de base populacional em São Paulo. Materiais e Métodos: O estudo é uma avaliação radiológica e análise quantitativa baseada em voxel com alinhamento de superfície de 525 imagens de ressonância magnética de participantes de uma coorte de idosos (SABE - Saúde, Bem-estar e Envelhecimento) em São Paulo, Brasil, com idades de 60 a 103 anos, dos dois sexos. Resultados: Observamos redução média do volume cerebral total de 2,4% por década após os 60 anos de idade. A redução de volume ocorreu na substância cinzenta e na substância branca com a idade. A relação entre volume cerebral intracraniano e volume cerebral total diferiu entre homens e mulheres. Conclusão: Nós reproduzimos os achados de estudos prévios em populações americanas e europeias. A relação entre volume intracraniano e volume cerebral é maior em homens, o que pode representar fonte de viés na avaliação de atrofia radiológica convencional, já que essa avaliação é usualmente baseada em análise de espaços liquóricos intracranianos.

Abstract Objective: To perform a quantitative analysis of the brain volume of elderly individuals in a population-based sample. Materials and Methods: This was a radiological assessment and voxel-based quantitative analysis, with surface alignment, of 525 magnetic resonance imaging scans of individuals between 60 and 103 years of age who participated in the Saúde, Bem-estar e Envelhecimento (Health, Well-being, and Aging) study in the city of São Paulo, Brazil. Results: We noted a median rate of reduction in total brain volume of 2.4% per decade after 60 years of age. Gray and white matter both showed volume reductions with age. The total brain volume/intracranial brain volume ratio differed between males and females. Conclusion: We have corroborated the findings of studies conducted in the United States and Europe. The total brain volume/intracranial brain volume ratio is higher in men, representing a potential bias for the conventional radiological assessment of atrophy, which is typically based on the evaluation of the cerebrospinal fluid spaces.

Abstract Our aim was to develop and apply a comprehensive noninvasive prenatal test (NIPT) by using high-coverage targeted next-generation sequencing to estimate fetal fraction, determine fetal sex, and detect trisomy and monogenic disease without parental genotype information. We analyzed 45 pregnancies, 40 mock samples, and eight mother-child pairs to generate 35 simulated datasets. Fetal fraction (FF) was estimated based on analysis of the single nucleotide polymorphism (SNP) allele fraction distribution. A Z-score was calculated for trisomy of chromosome 21 (T21), and fetal sex detection. Monogenic disease detection was performed through variant analysis. Model validation was performed using the simulated datasets. The novel model to estimate FF was robust and accurate (r2= 0.994, p-value < 2.2e-16). For samples with FF > 0.04, T21 detection had 100% sensitivity (95% CI: 63.06 to 100%) and 98.53% specificity (95% CI: 92.08 to 99.96%). Fetal sex was determined with 100% accuracy. We later performed a proof of concept for monogenic disease diagnosis of 5/7 skeletal dysplasia cases. In conclusion, it is feasible to perform a comprehensive NIPT by using only data from high coverage targeted sequencing, which, in addition to detecting trisomies, also make it possible to identify pathogenic variants of the candidate genes for monogenic diseases.

Abstract Neuromuscular disorders (NMD) are a heterogeneous group of genetic conditions, with autosomal dominant, recessive, or X-linked inheritance. They are characterized by progressive muscle degeneration and weakness. Here, we are presenting our major contributions to the field during the past 30 years. We have mapped and identified several novel genes responsible for NMD. Genotype-phenotype correlations studies enhanced our comprehension on the effect of gene mutations on related proteins and their impact on clinical findings. The search for modifier factors allowed the identification of a novel "protective"; variant which may have important implication on therapeutic developments. Molecular diagnosis was introduced in the 1980s and new technologies have been incorporated since then. Next generation sequencing greatly improved our capacity to identify disease-causing mutations with important benefits for research and prevention through genetic counseling of patients' families. Stem cells researches, from and for patients, have been used as tools to study human genetic diseases mechanisms and for therapies development. The clinical effect of preclinical trials in mice and canine models for muscular dystrophies are under investigation. Finally, the integration of our researches and genetic services with our post-graduation program resulted in a significant output of new geneticists, spreading out this expertise to our large country.

A paraplegia espástica, atrofia óptica e neuropatia (SPOAN) é uma forma complicada de paraplegia espástica de herança autossômica recessiva, caracterizada por atrofia óptica congênita, paraplegia espástica progressiva de início na infância e neuropatia periférica. Este estudo avaliou o desempenho motor e funcional de 61 indivíduos com SPOAN (5 a 72 anos), por meio do índice de Barthel modificado, a escala modificada de Ashworth, da avaliação da força de preensão das mãos com dinamômetro hidráulico de Jamar e escalas de paraplegia espástica hereditária. O índice de Barthel modificado, que investiga aspectos funcionais, mostrou-se mais sensível para avaliar a progressão da doença do que as escalas de paraplegia espástica. A espasticidade apresentou distribuição bimodal, com o grau 1 (mínimo) e 4 (máximo). A força de preensão mostrou correlação inversa moderada com a idade. A combinação de paraplegia espástica de início precoce com polineuropatia progressiva faz da SPOAN uma condição incapacitante.

Spastic paraplegia, optic atrophy, and neuropathy (SPOAN) is an autosomal recessive complicated form of hereditary spastic paraplegia, which is clinically defined by congenital optic atrophy, infancy-onset progressive spastic paraplegia and peripheral neuropathy. In this study, which included 61 individuals (age 5-72 years, 42 females) affected by SPOAN, a comprehensive motor and functional evaluation was performed, using modified Barthel index, modified Ashworth scale, hand grip strength measured with a hydraulic dynamometer and two hereditary spastic paraplegia scales. Modified Barthel index, which evaluate several functional aspects, was more sensitive to disclose disease progression than the spastic paraplegia scales. Spasticity showed a bimodal distribution, with both grades 1 (minimum) and 4 (maximum). Hand grip strength showed a moderate inverse correlation with age. Combination of early onset spastic paraplegia and progressive polyneuropathy make SPOAN disability overwhelming.

A distrofia muscular de Duchenne (DMD) é um tipo de distrofia muscular em humanos caracterizada por uma doença genética ligada ao cromossomo X. O cão golden retriever portador da distrofia muscular (GRMD) tem sido intensamente estudado e considerado o modelo mais representativo para a doença observada em humanos. Assim, como forma de verificar anormalidades em órgãos internos nesses animais, foi realizado o exame ultra-sonográfico de 24 cães golden retriever saudáveis, portadores e afetados pela distrofia muscular. O exame ultra-sonográfico do GRMD diagnosticou aumento hepático de moderado a severo, incluindo os vasos hepáticos e seus ramos e aumento de ecogenicidade da vesícula biliar e vesícula urinária. Entretanto, não foram observadas imagens claras de alterações no baço e nos vasos ramos da aorta. A partir disso, acreditamos que o exame ultra-sonográfico constitui-se em um procedimento útil no acesso de órgãos abdominais em cães afetados pela distrofia muscular.

Duchenne muscular dystrophy (DMD) is one type of human’s muscular dystrophy characterized by a genetic disorder linked to the X chromosome. The Golden Retriever muscular dystrophic (GRMD) has been extensively studied and considered the best resembling model to the human disease. Therefore, for identifying internal organs abnormality in GRMD, abdominal and pelvic ultrasonography was performed in 24 golden retriever dogs, either healthy or muscular dystrophic in different levels of disease. The GRMD ultrasonographic exams diagnosed moderate to severe liver enlargement, including hepatic vessels and their branches and increase of echogenicity in gallbladder and urinary bladder. However was not-clearly recognized pathologic images from spleen and aortic vessels were accessed. Therefore, we believe, the ultrasonographic exam was an useful procedure to the assessment of abdominal organs in dogs affected by muscular dystrophy.

OBJETIVO: Estudar a prevalência e a evolução natural dos eventos arrítmicos e distúrbios da condução, correlacionar o defeito genético com achados cardiovasculares, avaliar a mortalidade cardíaca, freqüência e fatores preditivos de morte súbita, correlacionar a gravidade do envolvimento neuromuscular e cardíaco e definir o papel do estudo eletrofisiológico (EEF), na distrofia miotônica. MÉTODOS: Realizados periodicamente avaliação clínica e exames complementares, exame genético, eletrocardiograma, ecocardiograma e Holter (exceto exame genético) em 83 pacientes consecutivos com tempo médio de seguimento de 42±30,63 meses, sendo o estudo eletrofisiológico realizado em 59 casos. RESULTADOS: Taquiarritmia atrial foi observada em 10 (12%) pacientes, taquicardia ventricular não sustentada (TVNS) em 14 (17%), bloqueio átrio-ventricular (BAV) 1º grau em 24 (29%), bloqueio de ramo esquerdo (BRE) em 19 (23%), bloqueio de ramo direito (BRD) em 13 (16%). Sintomas, aumento do intervalo PR, alargamento do QRS, fração de ejeção do ventrículo esquerdo (FEVE) <60% e idade foram preditivos de óbito. Ocorreram 9 mortes (4 súbitas; 2 insuficiência cardíaca; 3 outras). EEF: HV>70ms em 34% e >100ms em 11% (pós-procainamida). CONCLUSÃO: A prevalência dos eventos arrítmicos e distúrbios da condução foi de 50% a 80% após 6 anos, não se correlacionando ao defeito genético, sendo o flutter atrial, a arritmia sustentada mais freqüente. O envolvimento cardíaco aumentou com a piora da doença neuromuscular, mas essa progressão foi mais rápida que a neuromuscular. A mortalidade total foi baixa (11%) e morte súbita ocorreu em metade dos casos. EEF identificou grupo de risco para implante de marcapasso.

OBJECTIVE: To study the prevalence and natural evolution of arrhythmic events and conduction disturbances in myotonic dystrophy; to correlate the genetic defect with cardiovascular findings; to assess cardiac mortality, frequency, and predictive factors of sudden death; to correlate the severity of the neuromuscular and cardiac involvement; and to define the role of the electrophysiological study (EPS), in myotonic dystrophy. METHODS: Periodic clinical assessment and the following tests were performed in 83 consecutive patients with a mean follow-up of 42±30.63 months: complementary examinations, genetic tests, electrocardiography, echocardiography, and Holter; electrophysiological study was performed in 59 cases. RESULTS: Atrial tachyarrhythmia was observed in 10 (12%) patients, NSVT in 14 (17%), first-degree AVB in 24 (29%), LBBB in 19 (23%), and RBBB in 13 (16%). Symptoms, an increase in the PR interval, QRS enlargement, LVEF < 60%, and age were predictive factors of death. Nine patients died (4 sudden deaths; 2 due to heart failure; 3 due to other causes). Electrophysiological study: H-V interval >70 ms in 34% and > 100 ms in 11% (postprocainamide). CONCLUSION: The prevalence of arrhythmic events and conduction disturbances ranged from 50% to 80% after 6 years, and did not correlate with the genetic defect. Atrial flutter was the most common sustained arrhythmia. Cardiac involvement increased as the neuromuscular disease became aggravated, but progression of the cardiac involvement was more rapid than that of the neuromuscular disease. Overall mortality was low (11%) and sudden death occurred in half of the cases. The EPS identified a group at risk for pacemaker implantation.

APESAR do muito que se tem discutido, ainda existe muita confusão em relação aos conceitos de clonagem (reprodutiva e terapêutica) , células-tronco ( embrionárias e não embrionárias) e terapia celular bem como isso pode afetar as nossas vidas. Portanto a proposta desse artigo é o de tentar definir esses conceitos e expressar a minha posição sobre aspectos éticos não só como cientista mas também como representante de inúmeras famílias que vêem nessa nova tecnologia uma esperança futura de cura para inúmeras doenças neurodegenerativas , muitas vezes letais ou gravemente incapacitantes.

ALTHOUGH concepts such as human cloning (reproductive and therapeutic), stem cells (embryonic and non-embryonic) , and stem cell therapy and how these issues may affect our lives have been extensively discussed, there is still a lot of misunders-tanding. Therefore the aim of this article is to try to better explain these definitions and express my personal opinion on ethical aspects not only as a scientist but also as a representative of inumerous families who hope that this technology might represent in the future a treatment for many neurodegenerative disorders often lethal or severely disabling.

Congenital bilateral absence of the vas deferens (CBAVD) accounts for 1%-2% of sterility in men. A high incidence of mutations, as well as the involvement of the 5T variant of the T tract length in intron 8 of the cystic fibrosis conductance regulator (CFTR) gene, have been previously described in males with CBAVD. Herein we report the screening for mutations and for the 5T variant of the CFTR gene in 17 patients with CBAVD and three others with non-CABVD obstructive azoospermia. In the CBAVD group, three patients (15%) were compound heterozygotes for mutations, and five patients (25%) had a mutation in one allele and the 5T variant in the other; the 5T variant was also present in two other patients, one of them being homozygous. The most frequent mutation was DF508, present on five chromosomes (12.5%). A novel missense mutation (A399D) was detected in a Japanese CBVAD patient. Our results yield further evidence for a strong association between male obstructive azoospermia caused by CBAVD and mutation/5T variant in the CFTR gene. The search for CFTR mutations in such patients is thus recommended for genetic counseling of couples who undergo assisted fertilization due to CBAVD.

O fim do seqüenciamento do genoma humano levanta inúmeras questões: Como o projeto genoma humano vai influenciar nossas vidas? Como a medicina tem se beneficiado do estudo dos genes? Quais são as aplicações práticas imediatas e o que se espera para o futuro? Quais são as implicações éticas? Este capítulo ilustra como as doenças genéticas têm contribuído para a compreensão do genoma humano. Ajuda-nos a entender como nossos genes funcionam quando normais e por que causam doenças quando alterados. Do ponto de vista prático, o estudo dos genes tem permitido o diagnóstico molecular para um número crescente de patologias, o que é fundamental para evitar outros exames invasivos, identificar casais em risco, e prevenir o nascimento de novos afetados. Além disso, discute-se quais são as perspectivas futuras em relação ao tratamento destas e de outras patologias genéticas incluindo a clonagem para fins terapêuticos e a utilização de células-tronco. Finalmente aborda as implicações éticas relacionadas ao uso de testes genéticos. Os benefícios de cada teste, principalmente para doenças de início tardio para as quais ainda não há tratamento, têm que ser discutidos exaustivamente com os consulentes antes de sua aplicação.

The sequencing of the human genome raised many questions such as: How the human genome project will influence our lives? How the medicine will benefit from the study of genes ? What are the application in practice and what can we expect from the future? What are the ethical implications? This chapter illustrates how genetic diseases, such as neuromuscular disorders are contributing to our understanding of the human genome. It helps us to start to understand how our genes work and why they cause diseases when mutated. One of the practical application of studying genes is the improvement of molecular diagnosis for a growing number of disorders which is of utmost importance to avoid other invasive exams, identify "at risk" couples and prevent the birth of new cases (through genetic counseling and prenatal diagnosis). Potential new treatments for neuromuscular and other genetic disorders including therapeutic cloning, the use of stem cells and the ethical implication of genetic tests are also discussed. The benefit of each test, in particular for disorders of late onset for which there is still no treatment have to be exhaustively discussed with the consulents before their application

O fim do seqüenciamento do genoma humano levanta inúmeras questões: Como o projeto genoma humano vai influenciar nossas vidas? Como a medicina tem se beneficiado do estudo dos genes? Quais são as aplicações práticas imediatas e o que se espera para o futuro? Quais são as implicações éticas? Este capítulo ilustra como as doenças genéticas têm contribuído para a compreensão do genoma humano. Ajuda-nos a entender como nossos genes funcionam quando normais e por que causam doenças quando alterados. Do ponto de vista prático, o estudo dos genes tem permitido o diagnóstico molecular para um número crescente de patologias, o que é fundamental para evitar outros exames invasivos, identificar casais em risco, e prevenir o nascimento de novos afetados. Além disso, discute-se quais são as perspectivas futuras em relação ao tratamento destas e de outras patologias genéticas incluindo a clonagem para fins terapêuticos e a utilização de células-tronco. Finalmente aborda as implicações éticas relacionadas ao uso de testes genéticos. Os benefícios de cada teste, principalmente para doenças de início tardio para as quais ainda não há tratamento, têm que ser discutidos exaustivamente com os consulentes antes de sua aplicação.

The sequencing of the human genome raised many questions such as: How the human genome project will influence our lives? How the medicine will benefit from the study of genes ? What are the application in practice and what can we expect from the future? What are the ethical implications? This chapter illustrates how genetic diseases, such as neuromuscular disorders are contributing to our understanding of the human genome. It helps us to start to understand how our genes work and why they cause diseases when mutated. One of the practical application of studying genes is the improvement of molecular diagnosis for a growing number of disorders which is of utmost importance to avoid other invasive exams, identify "at risk" couples and prevent the birth of new cases (through genetic counseling and prenatal diagnosis). Potential new treatments for neuromuscular and other genetic disorders including therapeutic cloning, the use of stem cells and the ethical implication of genetic tests are also discussed. The benefit of each test, in particular for disorders of late onset for which there is still no treatment have to be exhaustively discussed with the consulents before their application

INTRODUÇÃO: A ataxia de Friedreich é uma doença neurodegenerativa e os critérios clínicos diagnósticos para os casos típicos incluem: a) idade de início precoce (< 20 ou 25 anos); b) herança autossômica recessiva; c) ataxia progressiva; e d) abolição dos reflexos tendinosos profundos. MÉTODOS: Estudou-se a freqüência e o tamanho das expansões GAA e a sua influência nos achados neurológicos, idade de início e progressão da doença, em 25 pacientes brasileiros com diagnóstico clínico de ataxia de Friedreich - 19 típicos e 6 atípicos, por PCR. RESULTADOS: Anormalidades sugestivas de comprometimento cerebelar, no ECG e a presença de pés cavos ocorreram com maior freqüência nos casos típicos; contudo, a resposta plantar e a fala mostraram-se mais freqüentemente normal neste grupo, quando comparados casos típicos e atípicos. A expansão GAA em homozigose foi detectada em 17 casos (68%) - todos típicos e, em 8 (32%) (6 atípicos e 2 típicos), não foi observada nenhuma expansão, excluindo-se o diagnóstico de ataxia de Friedreich. Deformidade de pés, anormalidades cardíacas e alguns achados neurológicos ocorreram mais freqüentemente, nos casos com expansão GAA, contudo, sinais de comprometimento dos pares cranianos e alterações dos achados tomográficos foram detectados menos frequentemente do que em pacientes sem expansão. DISCUSSÃO: A análise molecular é imprescindível para o diagnóstico de ataxia de Friedreich, não só para os casos típicos como também para os atípicos. Não há qualquer correlação entre o genótipo e o fenótipo. O diagnóstico baseado apenas nos achados clínicos é limitado, embora facilite a triagem para melhor selecionar os casos suspeitos que merecem ser testados. A dosagem sérica da vitamin E é recomendada , especialmente nos casos sem expansão GAA.

INTRODUCTION: Friedreich's ataxia is a neurodegenerative disorder whose clinical diagnostic criteria for typical cases basically include: a) early age of onset (< 20 or 25 years), b) autosomal recessive inheritance, c) progressive ataxia of limbs and gait, and d) absence of lower limb tendon reflexes. METHODS: We studied the frequency and the size of expanded GAA and their influence on neurologic findings, age at onset, and disease progression in 25 Brazilian patients with clinical diagnosis of Friedreich's ataxia - 19 typical and 6 atypical - using a long-range PCR test. RESULTS: Abnormalities in cerebellar signs, in electrocardiography, and pes cavus occurred more frequently in typical cases; however, plantar response and speech were more frequently normal in this group when the both typical and atypical cases were compared. Homozygous GAA expansion repeats were detected in 17 cases (68%) - all typical cases. In 8 patients (32%) (6 atypical and 2 typical), no expansion was observed, ruling out the diagnosis of Friedreich's ataxia. In cases with GAA expansions, foot deformity, cardiac abnormalities, and some neurologic findings occurred more frequently; however, abnormalities in cranial nerves and in tomographic findings were detected less frequently than in patients without GAA expansions. DISCUSSION: Molecular analysis was imperative for the diagnosis of Friedreich's ataxia, not only for typical cases but also for atypical ones. There was no genotype-phenotype correlation. Diagnosis based only on clinical findings is limited; however, it aids in better screening for suspected cases that should be tested. Evaluation for vitamin E deficiency is recommended, especially in cases without GAA expansion.

OBJETIVO: comparar as características clínicas de doença priônica com as da demência frontotemporal e parkinsonismo associada ao cromossoma 17 (FTDP-17). FUNDAMENTOS: doenças priônicas não são usualmente incluídas no diagnóstico diferencial da FTDP-17 porque a doença de Creutzfeldt-Jakob (DCJ), a mais comum entre as doenças priônicas hereditárias, frequentemente manifesta-se como demência rapidamente progressiva. Por outro lado, a FTDP-17 apresenta-se insidiosamente na quinta década, com alterações do comportamento e sinais parkinsonianos. MÉTODO: apresentamos as características clínicas de 12 membros de uma família com DCJ associada à mutação de ponto no codon 183 do gene da proteína priônica. RESULTADOS: os sintomas iniciaram-se aos 44.0 ± 3.7 anos e a duração até o óbito foi de dois a cinco anos. Alterações do comportamento foram os sintomas iniciais mais frequentes. Nove pacientes foram atendidos inicialmente por psiquiatras. Oito pacientes manifestaram sinais parkinsonianos. CONCLUSÃO: as características clínicas apresentam considerável semelhança com as descritas na FTDP-17.

OBJECTIVE: To compare the clinical features of a familial prion disease with those of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). BACKGROUND: Prion diseases are not usually considered in the differential diagnosis of FTDP-17, since familial Creutzfeldt-Jakob disease (CJD), the most common inherited prion disease, often manifests as a rapidly progressive dementia. Conversely, FTDP-17 usually has an insidious onset in the fifth decade, with abnormal behavior and parkinsonian features. METHOD: We present the clinical features of 12 patients from a family with CJD associated with a point mutation at codon 183 of the prion protein gene. RESULTS: The mean age at onset was 44.0 ± 3.7; the duration of the symptoms until death ranged from two to nine years. Behavioral disturbances were the predominant presenting symptoms. Nine patients were first seen by psychiatrists. Eight patients manifested parkinsonian signs. CONCLUSION: These clinical features bear a considerable resemblance to those described in FTDP-17.