Navegando por Palavras-chave "Phenotype"

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    Als5/spg11/kiaa1840 mutations cause autosomal recessive axonal charcot-marie-tooth disease
    (Oxford univ press, 2016) Montecchiani, Celeste; Pedace, Lucia; Lo Giudice, Temistocle; Casella, Antonella; Mearini, Marzia; Gaudiello, Fabrizio; Pedroso, Jose Luiz [UNIFESP]; Terracciano, Chiara; Caltagirone, Carlo; Massa, Roberto; St George-Hyslop, Peter H.; Barsottini, Orlando Graziani Povoas [UNIFESP]; Kawarai, Toshitaka; Orlacchio, Antonio
    Charcot-Marie-Tooth disease is a group of hereditary peripheral neuropathies that share clinical characteristics of progressive distal muscle weakness and atrophy, foot deformities, distal sensory loss, as well as diminished tendon reflexes. Hundreds of causative DNA changes have been found, but much of the genetic basis of the disease is still unexplained. Mutations in the ALS5/SPG11/KIAA1840 gene are a frequent cause of autosomal recessive hereditary spastic paraplegia with thin corpus callosum and peripheral axonal neuropathy, and account for similar to 40% of autosomal recessive juvenile amyotrophic lateral sclerosis. The overlap of axonal Charcot-Marie-Tooth disease with both diseases, as well as the common autosomal recessive inheritance pattern of thin corpus callosum and axonal Charcot-Marie-Tooth disease in three related patients, prompted us to analyse the ALS5/SPG11/KIAA1840 gene in affected individuals with autosomal recessive axonal Charcot-Marie-Tooth disease. We investigated 28 unrelated families with autosomal recessive axonal Charcot-Marie-Tooth disease defined by clinical, electrophysiological, as well as pathological evaluation. Besides, we screened for all the known genes related to axonal autosomal recessive Charcot-Marie-Tooth disease (CMT2A2/HMSN2A2/MFN2, CMT2B1/LMNA, CMT2B2/MED25, CMT2B5/NEFL, ARCMT2F/dHMN2B/HSPB1, CMT2K/GDAP1, CMT2P/LRSAM1, CMT2R/TRIM2, CMT2S/IGHMBP2, CMT2T/HSJ1, CMTRID/COX6A1, ARAN-NM/HINT and GAN/GAN), for the genes related to autosomal recessive hereditary spastic paraplegia with thin corpus callosum and axonal peripheral neuropathy (SPG7/PGN, SPG15/ZFYVE26, SPG21/ACP33, SPG35/FA2H, SPG46/GBA2, SPG55/C12orf65 and SPG56/CYP2U1), as well as for the causative gene of peripheral neuropathy with or without agenesis of the corpus callosum (SLC12A6). Mitochondrial disorders related to Charcot-Marie-Tooth disease type 2 were also excluded by sequencing POLG and TYMP genes. An additional locus for autosomal recessive Charcot-Marie-Tooth disease type 2H on chromosome 8q13-21.1 was excluded by linkage analysis. Pedigrees originated in Italy, Brazil, Canada, England, Iran, and Japan. Interestingly, we identified 15 ALS5/SPG11/KIAA1840 mutations in 12 families (two sequence variants were never reported before, p.Gln198* and p.Pro2212fs*5). No large deletions/duplications were detected in these patients. The novel mutations seemed to be pathogenic since they co-segregated with the disease in all pedigrees and were absent in 300 unrelated controls. Furthermore, in silico analysis predicted their pathogenic effect. Our results indicate that ALS5/SPG11/KIAA1840 is the causative gene of a wide spectrum of clinical features, including autosomal recessive axonal Charcot-Marie-Tooth disease.
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    Caracterização da regeneração, inflamação e estresse oxidativo no músculo de modelo experimental para distrofia muscular de Duchenne com fenótipo exacerbado pelo exercício
    (Universidade Federal de São Paulo, 2021-05-12) Lazzarin, Mariana Cruz [UNIFESP]; De Oliveira, Flavia [UNIFESP]; http://lattes.cnpq.br/3387760393535776; http://lattes.cnpq.br/1579497511371132; Universidade Federal de São Paulo (UNIFESP)
    Introdução: A distrofia muscular de Duchenne é uma doença caracterizada por necrose muscular progressiva. O avanço das intervenções terapêuticas e das terapias genéticas tem trazido esperanças quanto à manutenção da funcionalidade motora mesmo em estágios mais tardios da doença. Entretanto, um grande desafio na prescrição de exercícios na reabilitação física para esses pacientes é a ausência de um perfil abrangente da resposta do músculo distrófico ao exercício. Dessa forma, o objetivo desse trabalho foi compreender, em camundongos mdx com fenótipo exacerbado pelo exercício, parâmetros relacionados à regeneração muscular, à inflamação e ao estresse oxidativo. Materiais e métodos: Camundongos C57BL/10 e C57BL/10-DMDmdx, com seis meses de vida, distribuídos em três grupos (n=10 cada): Controle, Mdx e Mdx+Exercício. O protocolo de corrida em declive foi de sete semanas, com frequência de cinco vezes na semana, a uma velocidade máxima particular para cada animal durante 60 minutos. Após eutanásia, o m. gastrocnêmio foi dissecado e realizou-se as análises: histopatológica; imunoistoquímica para marcadores de regeneração muscular (MyoD e Miogenina), de inflamação (COX-2) e para estresse oxidativo (8-OHdG); expressão de genes (qPCR) de NF-kB e NADP(H) Oxidase 2. Resultados: O grupo Mdx+Exercício apresentou a histopatologia do m. gastrocnêmio alterada pela corrida em declive, com maior incidência de fibrose endomisial e menor porcentagem de área de mionecrose. A análise imunoistoquímica revelou aumento da imunoexpressão de Miogenina no grupo Mdx+Exercício, mesmo não influenciando a expressão de MyoD; menor imunoexpressão do 8-OHdG no grupo Mdx e alterou a região histopatológica com imunoexpressão da COX-2. No grupo Mdx, a COX-2 estava relacionada com áreas de regeneração e infiltrado inflamatório, enquanto que no grupo Mdx+Exercício estava associado a regiões de fibrose muscular. Além disso, o exercício não influenciou a expressão gênica de NF-kB, porém aumentou o RNAm de NAD(P)H Oxidase 2. Conclusão: A exacerbação do fenótipo da DMD no músculo gastrocnêmio de camundongos mdx adultos está associada com o aumento da Miogenina, da COX-2 em regiões de fibrose e do 8-OHdG nuclear, bem como da expressão gênica de NAD(P)H Oxidase 2.
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    Dor e funcionalidade em pacientes com diferentes graus de osteartrite de joelho (OAJ)
    (Universidade Federal de São Paulo (UNIFESP), 2018) Pedrão, Gabriel Augusto [UNIFESP]; Pinfildi, Carlos Eduardo [UNIFESP]; Sardim, André Cabral [UNIFESP]; http://lattes.cnpq.br/8003125014433323; http://lattes.cnpq.br/6370481853776867; http://lattes.cnpq.br/9498843615233029; Universidade Federal de São Paulo (UNIFESP)
    Introdução: A osteoartrite de joelho (OAJ) é uma das doenças ortopédicas mais prevalentes e afeta até um terço da população idosa. Tem como principal sintoma a dor e afeta diretamente a qualidade de vida e funcionalidade dos pacientes dependendo da evolução, caracterizada em graus, segundo Kellgren-Lawrence. Porém, clinicamente pode haver diferenças entre o grau radiográfico e sintomas dos pacientes com OAJ. Objetivo: Avaliar a intensidade da dor e funcionalidade em pacientes com diferentes graus de OAJ. Método: Participarão do estudo pacientes de ambos os gêneros diagnosticados com OAJ unilateral ou bilateral com classificação de Kellgren-Lawrence (KL) grau I, II, III e IV por meio de radiografia. Estes pacientes serão submetidos as seguintes avaliações: questionário de qualidade de vida (WHOQOL-abreviado), questionário funcional para o joelho (KOOS), escala numérica de dor (END), limiar de dor por pressão (PPT), questionário para dor neuropática (LANSS), plataforma de força (equilíbrio), sit-to-stand test (STS) e timed up and go test (TUG). Resultados: O Grau IV obteve os maiores valores no TUG e END além dos menores valores no KOOS, STS e qualidade de vida e aspectos físicos do WHOQOL. O Grau I obteve os menores valores no TUG e END, além dos maiores valores no STS, WHOQOL e KOOS. Conclusão: Tanto a dor quanto a funcionalidade apresentam piora com a progressão da osteoartrite de joelho
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    Efeito da bradicinina na reatividade vascular sob influência do fenótipo da enzima conversora de angiotensina I (ECA - E.C. 3.4.15.1)
    (Universidade Federal de São Paulo (UNIFESP), 2017-07-31) Guimarães, Thales Henrique Santos [UNIFESP]; Landman, Maria Teresa Riggio de Lima [UNIFESP]; http://lattes.cnpq.br/8687378770717503; http://lattes.cnpq.br/3147571376928164; Universidade Federal de São Paulo (UNIFESP)
    In previous studies of the group, it was found that female rats from 2-BAW colony features the plasma angiotensin-converting enzyme (ACE) activity with very outliers, but constant for each animal. This fact made it possible to divide these animals into three groups according to the levels of this enzyme: animals with high ACE activity (ECAa), with intermediate ACE activity (ECAi) and low ACE activity (ECAb). Heredity phenotypes were proven, which led to the establishment of a new strain of animals: Wistar/INFAR/ECAa and Wistar/INFAR/ECAb. However, The blood pressure of the animals, were not different between the phenotypes, a puzzling fact taking into account the participation of the renin-angiotensin-aldosterone system (RAAS) and the kallikrein-kinin system (KKS) in maintaining blood pressure. From these data, this study aims to analyze the effect of bradykinin and other kinins in the vascular reactivity of these rats with different phenotypes of ACE using agonists and antagonists of the parasympathetic nervous system (SNP), RAAS and KKS. Therefore, we evaluated the participation of these systems in vitro in thoracic aorta of male rats ECAa and ECAb. In the study of acetylcholine in the presence and absence of atropine it was not possible to detect significant differences between phenotypes and in the presence of atropine, showed a vasodilator concentration-dependent blocked response. In the analysis of the KKS using bradykinin (BK), we observed a similar hypotensive effect between phenotypes and when preincubated the B2 receptor antagonist of bradykinin (HOE-140), we observed a significant reduction of the vasodilatory effect (Emax) concentration-dependent, indicating thus the response of bradykinin might be mediated mainly via the B2 receptor. Also about bradykinin, we found that its action takes place predominantly via nitric oxide (NO) because when pre-incubated the NOS inhibitor (L-NAME), a significant reduction of vasorelaxant response was observed, but again, with no significant differences between phenotypes. It was also studied the action of des-Arg9-BK, an active BK-metabolite, which was possible to observe a response very similar to BK, although with a lower Emax, thus suggesting a lower affinity and activation of the B2 receptor, which is expressed constitutively. In the study of phosphorylated kinin we observed a decreased response of the phophorylated bradykinin compared to non-phosphorylated form, indicating a direct effect of the phosphate group (-PO3H2) in the interaction and activation of kinin receptors. Finally, we determined the vasodilator response of Ang (1-7), as well as its influence on bradykinin, which potentiated the vasodilatory action of BK, but with no differences between the phenotypes. In conclusion, the findings of this study serve to highlight that although these animals have different phenotypes (ECAa, ECAb), they do not have distinct responses to these vasodilators, ie the enzymatic phenotypes of ACE does not seem to influence the final responses of the vasoactive substances studied, due possibly exist compensatory mechanisms by alternative pathways different of the RAAS and KKS.
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    Exoma na prática clínica: expansão fenotípica, dismorfologia reversa e descoberta de novos genes
    (Universidade Federal de São Paulo (UNIFESP), 2016-12-21) Migliavacca, Michele Patricia [UNIFESP]; Perez, Ana Beatriz Alvarez [UNIFESP]; http://lattes.cnpq.br/4784102068388854; http://lattes.cnpq.br/8551223548156991; Universidade Federal de São Paulo (UNIFESP)
    Purpose: To analyze candidate variants for previous selected patients with Mendelian Diseases using Whole Exome Sequencing (WES). Methods: Patients were obtained from PhenoDB platform and reviewed by a Committee. Those who filled in the selection criteria had the exome sequencing performed by the Illumina HiSeq2000 (Illumina, Inc. San Diego, CA) platform. The data analysis workflow was design to evaluate possible candidate variants using specific computational filters. The ANNOVAR file of each patient was uploaded at the PhenoDb platform being available to the Analysis Committee. Results: Twelve patients that better represented one of the following categories was selected: new gene discovery, phenotypic expansion and reverse dysmorphology. A cohort of six patients were selected to represent the category of new gene discovery, all of them shared the same clinical diagnosis of Gomez-Lopez-Hernandez Syndrome (OMIM 601853, a mendelian disease without a known molecular basis, unfurtunally no candidate variants were found to the moment; a patient with Van den Ende Gupta Syndrome and a SCARF2 homozygous 17bp deletion and a new finding, bilateral sclerocornea, thus extending the phenotype; one patient with severe neonatal ichthyosis and limb malformation, unusual findings in assotiation, with a new mutation at the MBTPS2 responsible for the BRESHECK Syndrome; one patient with a previous clinical diagnosis of Ramos-Arroyo Syndrome and a pathogenic variant at the BCOR gene related to Syndromic Microophtalmya type 2; one brother and one sister with compound heterozygous mutation at the ERCC3 gene, with an overlapping phenotype of Tricothiodystrophy and Xeroderma Pigmentosum, and a patient with a pathogenic variant at HDAC8 gene responsible for Cornelia de Lange type 5 Syndrome. Conclusion: WES is a valid approach to investigated mendelian diseases when a molecular basis is not known, genetic heterogeneity plays a important role or if there is a suggestive mendelian inheritance without a clear diagnosis.
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    Frequência e distribuição corpórea dos nevos melanocíticos adquiridos na população de 2 a 18 anos de idade que frequentam creches ou escolas públicas, residentes em Votuporanga, Estado de São Paulo
    (Universidade Federal de São Paulo (UNIFESP), 2003) Yarak, Samira [UNIFESP]; Almeida, Fernando Augusto de [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Objetivo: Avaliar, por meio de estudo epidemiologico, a frequencia e a distribuicao corporea dos nevos melanociticos adquiridos (NMA) e observar a influencia das variaveis ambientais e constitucionais nos fenotipos heterogeneos, em uma regiao geografica de intensa exposicao solar. Metodos: Foi realizado estudo transversal das frequencias absoluta e relativa dos NMA de todos os tamanhos, com a inclusao de todas as regioes anatomicas padronizadas pelo protocolo internacional (IARCI OMS, 1990), em 1.279 criancas e adolescentes, com idades de 2 a 18 anos, de creches e escolas publicas na cidade de Votuporanga (20°S), São Paulo, Brasil. Resultados: Setenta e cinco por cento dos individuos apresentaram ate 13 nevos, 50 por cento ate seis nevos e 5 por cento mais de 30 nevos. A contagem de NMA de todos os tamanhos foi mais alta nas regioes toracica e abdominal superior, ombros, face e dorso. Os membros superiores apresentaram mais NMA do que os membros inferiores e houve baixa contagem de NMA nas maos e nos pes. O sexo feminino apresentou quantidade de NMA estatisticamente semelhante ao sexo masculino. As mulheres apresentaram maior contagem de NMA nas faces externas dos membros superiores, face interna do membro superior direito, faces anteriores e posteriores dos membros inferiores, e gluteos. Os homens apresentaram maior contagem de NMA na regiao posterior do pescoco. Observou-se aumento progressivo da contagem de NMA com a idade, com picos aos 13 e aos 16 anos. As regioes de exposicao solar apresentaram maior numero de NMA de maiores diametros (ombros, torax, abdome superior, face e dorso). Os tamanhos dos NMA apresentaram correlacao com a idade, exceto para os gluteos, faces internas dos membros superiores e face posterior da perna direita. Houve forte correlacao entre o numero de NMA e o complexo de pele tipo 3. Exposicao solar, cor dos cabelos e dos olhos, efelides e queimadura solar, tambem apresentaram associacao com alta contagem dos NMA. Conclusoes: Os NMA estao distribuidos por toda a superficie corporal, e em maior numero e tamanho nas regioes de exposicao solar. O aparecimento precoce dos NMA, a distribuicao corporea e a contagem baixa de NMA na populacao heterogenea sustentam a hipotese de que a miscigenacao racial e as regioes anatomicas especificas apresentam diferencas no potencial de proliferacao dos nevos
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    Identificação de regiões cromossômicas e genes candidatos em pacientes com características fenotípicas do espectro oculoauriculovertebral (OAVS)
    (Universidade Federal de São Paulo (UNIFESP), 2016-12-14) Colovati, Mileny Esbravatti Stephano [UNIFESP]; Melaragno, Maria Isabel de Souza Aranha [UNIFESP]; Perez, Ana Beatriz Alvarez [UNIFESP]; http://lattes.cnpq.br/4784102068388854; http://lattes.cnpq.br/0678071850781758; http://lattes.cnpq.br/4285129475265961; Universidade Federal de São Paulo (UNIFESP)
    O espectro oculoauriculovertebral (OAVS, OMIM%164210) é um conjunto de doenças envolvendo alterações durante o desenvolvimento dos primeiro e segundo arcos faríngeos na embriogênese. Essa condição clínica é caracterizada por um espectro de alterações fenotípicas incluindo, alterações de orelhas, microssomia hemifacial, defeitos oculares, perda auditiva, fendas orofaciais, deficiência intelectual e malformações vertebrais. A maioria dos casos são esporádicos e sua etiologia não é bem conhecida. Alguns estudos de análise de segregação relataram loci candidatos para OAVS, mas apenas o gene MYT1 tem sido consistentemente associado a esse espectro. Alterações cromossômicas têm sido identificadas, algumas recorrentes, sendo a região cromossômica 22q11.2 a mais frequentemente envolvida. Avaliamos citogenomicamente 75 pacientes com OAVS, sendo 60 casos esporádicos os demais pertencentes a seis famílias. A maioria dos pacientes apresentaram cariótipos normais, com exceção de duas pacientes, uma com inversão paracêntrica no cromossomo 12 e outra com um cromossomo marcador adicional em mosaico, achados que não foram relacionados ao OAVS. Uma paciente apresentou um derivado do cromossomo 4 da translocação materna t(X;4)(p22.31;p15.33) detectada somente por array e FISH, tendo os pontos de quebra do rearranjo sequenciados. Os resultados de array genômico dos 75 pacientes, quando comparados aos bancos de dados e literatura, revelaram 21 CNVs (copy number variations) em 20 diferentes pacientes. Dentre essas, sete eram deleções e quatorze eram duplicações. Os resultados obtidos não apontaram uma região genômica alterada única relacionada com a doença em estudo, mas rearranjos cromossômicos recorrentes foram observados nas regiões 4p16.1, 22q11.2 e Xp22.33. As CNVs consideradas patogênicas ou VOUS (variants of unknown significance) possivelmente patogênicas incluem ou estão próximas aos genes com relevância para o fenótipo do OAVS e/ou doenças conhecidas. A identificação de rearranjos na região 22q11 em alguns dos nossos pacientes reforça a hipótese de que essa região é um locus candidato. Além disso, a recorrência de CNVs no cromossomo 4p16.1, em três pacientes, revelou outra região relevante para o fenótipo e um novo gene candidato, o HMX1. Em colaboração com um grupo francês, identificamos em uma paciente a terceira mutação descrita no gene MYT1, relatado como responsável pela síndrome de Goldenhar. Portanto, a investigação das regiões cromossômicas e a identificação de genes candidatos em pacientes com o fenótipo OAVS podem, potencialmente, sugerir diferentes mecanismos patogênicos envolvidos nesse espectro fenotipicamente e geneticamente heterogêneo.
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    Immunohistochemical analysis of retinoblastoma cell phenotype using neuronal and glial cell markers
    (Consel Brasil Oftalmologia, 2016) Orellana, Maria Eugenia; Belfort, Rubens Neto [UNIFESP]; Antecka, Emilia; Burnier Júnior, Miguel Noel Nascente [UNIFESP]
    Purpose: The cellular origin of retinoblastoma is uncertain as constituent tumor cells heterogeneously express markers of both immature and mature retinal cells. An immunohistochemical analysis of cellular origin may yield valuable insights into disease progression and treatment options. This study aimed to determine the cellular origin of retinoblastoma in a large case series and correlate these findings with histopathological prognostic factors. Methods: Thirty-nine retinoblastoma cases were histopathologically diagnosed and analyzed by immunohistochemistry using monoclonal antibodies against the immature neural cell marker SRY-box containing gene 2 (SOX-2), the mature neuronal cell marker microtubule-associated protein 2 (MAP2), and the mature glial cell marker glial fibrillary acidic protein (GFAP). Histopathological features were also evaluated, including patterns of growth, differentiation, vitreous see-ding, and choroidal/scleral, optic nerve, and anterior chamber invasion. Two retinoblastoma cell lines, WERI-1 and Y79, were studied by immunocytochemistry using the same antibodies. Results: Expression of SOX-2 was strong in 97.4% of retinoblastoma cases, while MAP-2 was expressed in 59% of cases. Immunostaining for GFAP was positive only in reactive stromal astrocytes interspersed amongst tumor cells and in peritumoral tissue. There was no correlation between histopathological prognostic factors and immunohistochemical markers. Retinoblastoma cell lines showed strong positivity for SOX2 (90% of WERI-1 cells and 70% of Y79 cells) and MAP2 (90% of cells in both lines). GFAP was completely negative in both cell lines. Conclusion: The majority of retinoblastomas and both RB cell lines expressed an immature neural and/or a mature neuronal cell marker, but not a glial marker. These results indicate a typical neuroblast or neuronal origin and eliminate astrocyte differentiation from neural stem cells as the source of retinoblastoma.
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    Late-onset obsessive-compulsive disorder: Risk factors and correlates
    (Elsevier B.V., 2014-02-01) Frydman, Ilana; Brasil, Pedro E. do; Torres, Albina R.; Shavitt, Roseli G.; Ferrao, Ygor A.; Rosario, Maria C. [UNIFESP]; Miguel, Euripedes C.; Fontenelle, Leonardo F.; Universidade Federal do Rio de Janeiro (UFRJ); DOr Inst Res & Educ; Univ Estadual Paulista; Universidade de São Paulo (USP); Hlth Sci Fed Univ Porto Alegre; Universidade Federal de São Paulo (UNIFESP); Universidade Federal Fluminense (UFF)
    Background: While a great amount of attention has been paid to early-onset obsessive-compulsive disorder (OCD), there is a dearth of studies on patients showing OCD for the first time at later stages of life. in this study, we aimed at determining possible risk factors/correlates for OCD onset at or after age 40, here termed late-onset OCD.Method: A series of models including several potential variables associated with late onset OCD were tested using a monolayer neural network. To this regard, data from the Brazilian Research Consortium of Obsessive-Compulsive Spectrum Disorders (CTOC) (n = 1001) was employed. for the purposes of this study, we considered a diagnosis of late onset OCD to be present whenever distress and interference associated with OCD symptoms emerged at or after age 40. Different nested models were compared through the Akaike Criteria keeping the variables with p value <= 0.05.Results: Late-onset OCD occurred in 8.6% of the sample. A model including female sex, a history of chronic (>10 years) subclinical obsessive-compulsive symptoms, the co-occurrence of posttraumatic stress disorder (PTSD) after age 40, and a history of recent pregnancy in self or significant others was able to explain a sizeable proportion of late-onset OCD. the general performance of this model, represented by the Maximum Likelihood R2, was 29.4%.Conclusion: Our results suggest that late-onset OCD is more likely to occur in females, in individuals with long periods of subclinical obsessive-compulsive symptoms, and in association with a major traumatic event occurring after age 40 and a history of recent pregnancy in self or in significant others. (C) 2013 Elsevier B.V. All rights reserved.
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    Phenotypic spectrum of FARS2-deficiency
    (Elsevier Science Bv, 2018) Finsterer, Josef; Scorza, Carla Alessandra [UNIFESP]; Scorza, Fulvio Alexandre [UNIFESP]
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    Quantifying dimensional severity of obsessive-compulsive disorder for neurobiological research
    (Pergamon-Elsevier Science Ltd, 2017) Shavitt, Roseli G.; Requena, Guaraci; Alonso, Pino; Zai, Gwyneth; Costa, Daniel L. C.; de Braganca Pereira, Carlos Alberto; do Rosario, Maria Conceicao [UNIFESP]; Morais, Ivanil; Fontenelle, Leonardo; Cappi, Carolina; Kennedy, James; Menchon, Jose M.; Miguel, Euripedes; Richter, Peggy M. A.
    Current research to explore genetic susceptibility factors in obsessive-compulsive disorder (OCD) has resulted in the tentative identification of a small number of genes. However, findings have not been readily replicated. It is now broadly accepted that a major limitation to this work is the heterogeneous nature of this disorder, and that an approach incorporating OCD symptom dimensions in a quantitative manner may be more successful in identifying both common as well as dimension-specific vulnerability genetic factors. As most existing genetic datasets did not collect specific dimensional severity ratings, a specific method to reliably extract dimensional ratings from the most widely used severity rating scale, the Yale-Brown Obsessive Compulsive Scale (YBOCS), for OCD is needed. This project aims to develop and validate a novel algorithm to extrapolate specific dimensional symptom severity ratings in OCD from the existing YBOCS for use in genetics and other neurobiological research. To accomplish this goal, we used a large data set comprising adult subjects from three independent sites: the Brazilian OCD Consortium, the Sunnybrook Health Sciences Centre in Toronto, Canada and the Hospital of Bellvitge, in Barcelona, Spain. A multinomial logistic regression was proposed to model and predict the quantitative phenotype [i.e., the severity of each of the five homogeneous symptom dimensions of the Dimensional YBOCS (DYBOCS)] in subjects who have only YBOCS (categorical) data. YBOCS and DYBOCS data obtained from 1183 subjects were used to build the model, which was tested with the leave-one-out cross-validation method. The model's goodness of fit, accepting a deviation of up to three points in the predicted DYBOCS score, varied from 78% (symmetry/order) to 84% (cleaning/contamination and hoarding dimensions). These results suggest that this algorithm may be a valuable tool for extracting dimensional phenotypic data for neurobiological studies in OCD.
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    Symptom dimensions, clinical course and comorbidity in men and women with obsessive-compulsive disorder
    (Elsevier B.V., 2013-09-30) Torresan, Ricardo C.; Ramos-Cerqueira, Ana Teresa A.; Shavitt, Roseli G.; Rosario, Maria Conceicao do [UNIFESP]; Mathis, Maria Alice de; Miguel, Euripedes C.; Torres, Albina R.; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)
    The study aimed to compare male and female patients with obsessive-compulsive disorder (OCD) across symptom dimensions, clinical course and comorbidity. A cross-sectional study was undertaken with 858 adult OCD patients (DSM-IV) from the Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders. Patients were evaluated using structured interviews, including the Dimensional Yale-Brown Obsessive-Compulsive Scale (DY-BOCS) and the Structured Clinical Interview for DSM-IV Axis I disorders (SCID-I). the sample was composed of 504 women (58.7%) and 354 men (41.3%) with a mean age of 35.4 years-old (range: 18-77). Men were younger, more frequently single and presented more tics, social phobia and alcohol use disorders. Among men, symptom interference occurred earlier and symptoms of the sexual/religious dimension were more common and more severe. Conversely, women were more likely to present symptoms of the aggressive, contamination/cleaning and hoarding dimension and comorbidity with specific phobias, anorexia nervosa, bulimia, trichotillomania, skin picking and compulsive buying. in the logistic regression, female gender remained independently associated with the aggressive and contamination/cleaning dimensions. in both genders the aggressive dimension remained associated with comorbid post-traumatic stress disorder, the sexual/religious dimension with major depression and the hoarding dimension with tic disorders. Gender seems to be relevant in the determination of OCD clinical presentation and course and should be considered an important aspect when defining more homogeneous OCD subgroups. (c) 2012 Elsevier Ireland Ltd. All rights reserved.
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    Trajectory in obsessive-compulsive disorder comorbidities
    (Elsevier B.V., 2013-07-01) Mathis, Maria Alice de; Diniz, Juliana B.; Hounie, Ana G.; Shavitt, Roseli G.; Fossaluza, Victor; Ferrao, Ygor; Leckman, James F.; Pereira, Carlos de Braganca; Rosario, Maria Conceicao do [UNIFESP]; Miguel, Euripedes C.; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP); Obsess Compuls Disorder Brazilian Consortium C TO; Yale Univ
    The main goal of this study is to contribute to the understanding of the trajectory of comorbid disorders associated with obsessive-compulsive disorder (OCD) according to the first manifested psychiatric disorder and its impact in the clinical course of OCD and subsequent psychiatric comorbidities. One thousand and one OCD patients were evaluated at a single time point. Standardized instruments were used to determine the current and lifetime psychiatric diagnoses (Structured Clinical Interview for DSM-IV Axis I and for impulse-control disorders) as well as to establish current obsessive-compulsive, depressive and anxiety symptom severity (Yale-Brown Obsessive-Compulsive Scale; Dimensional Yale-Brown Obsessive-Compulsive Scale, Beck Depression and Anxiety Inventories and the OCD Natural History Questionnaire). To analyze the distribution of comorbidities according to age at onset Bayesian approach was used. Five hundred eight patients had the first OC symptom onset till the age of 10 years old. the first comorbidity to appear in the majority of the sample was separation anxiety disorder (17.5%, n=175), followed by ADHD (5.0%, n=50) and tic disorders (4.4%, n=44). OCD patients that presented with separation anxiety disorder as first diagnosis had higher lifetime frequency of post-traumatic stress disorder (p=0.003), higher scores in the Sexual/Religious dimension (p=0.04), Beck Anxiety (p<0.001) and Depression (p=0.005) Inventories. OCD patients that initially presented with ADHD had higher lifetime frequencies of substance abuse and dependence (p<0.001) and worsening OCD course (p=0.03). OCD patients that presented with tic disorders as first diagnosis had higher lifetime frequencies of OC spectrum disorders (p=0.03). OCD is a heterogeneous disorder and that the presence of specific comorbid diagnoses that predate the onset of OCD may influence its clinical presentation and course over the lifetime. (C) 2012 Elsevier B.V. and ECNP. All rights reserved.
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    Wolf-hirschhorn syndrome with epibulbar dermoid: an unusual association in a patient with 4p deletion and functional xp disomy
    (Esmon Publicidad S A, 2016) Bragagnolo, Silvia; Colovati, Mileny E. S.; Guilherme, Roberta S.; Dantas, Anelisa G.; de Souza, Malu Zamariolli; de Soares, Maria F.; Melaragno, Maria I.; Perez, Ana B.
    Wolf-Hirschhorn syndrome (WHS) is a contiguous gene and multiple malformation syndrome that results from a deletion in the 4p16.3 region. We describe here a 6-month-old girl that presented with WHS features but also displayed unusual findings, such as epibulbar dermoid in the left eye, ear tags, and left microtia. Although on G-banding her karyotype appeared to be normal, chromosomal microarray analysis revealed an similar to 13-Mb 4p16.3p15.33 deletion and an similar to 9-Mb Xp22.33p22.31 duplication, resulting from a balanced maternal t(X