RESUMO
The role of some genes and their single nucleotide polymorphisms (SNPs) as genetic contributors of complex diseases is still a topic of much investigation. Research on genes related to autism susceptibility has been somewhat challenging, but also promising. Common genomic variants of CNTNAP2 have been associated with autism, and a range of autistic phenotypes such as impaired language function, abnormal social behavior, intellectual deficiency, epilepsy, and schizophrenia have been associated with this gene. Earlier findings have suggested that SNPs in the CNTNAP2 gene may be used as genetic markers for predisposition to autism spectrum disorder (ASD). We analyzed the SNPs (rs7794745 and rs2710102) in the CNTNAP2 gene of 210 individuals with idiopathic ASD and 200 non-autistic individuals by polymerase chain reaction-restriction fragment length polymorphism. The results revealed higher frequency distributions statistically significant (P = 0.034) of the homozygous SNP rs7794745 (presumed risk genotype) in ASD patients as compared with control subjects. The results also showed an association (OR = 1.802, 95%CI = 1.054-3.083, P = 0.042) between the same homozygous genotype and ASD, suggesting that it is a susceptibility factor for autism in this Brazilian population.
Assuntos
Transtorno do Espectro Autista/metabolismo , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Transtorno do Espectro Autista/genética , Brasil , Criança , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , MasculinoRESUMO
OBJECTIVES: We investigated the association between non-syndromic oral cleft and variants in IRF6 (rs2235371 and rs642961) and 8q24 region (rs987525) according to the ancestry contribution of the Brazilian population. SUBJECTS AND METHODS: Subjects with oral cleft (CL, CLP, or CP) and their parents were selected from different geographic regions of Brazil. Polymorphisms were genotyped using a TaqMan assay and genomic ancestry was estimated using a panel of 48 INDEL polymorphisms. RESULTS: A total of 259 probands were analyzed. A TDT detected overtransmission of the rs2235371 G allele (P = 0.0008) in the total sample. A significant association of this allele was also observed in CLP (P = 0.0343) and CLP + CL (P = 0.0027). IRF6 haplotype analysis showed that the G/A haplotype increased the risk for cleft in children (single dose: P = 0.0038, double dose: P = 0.0022) and in mothers (single dose: P = 0.0016). The rs987525 (8q24) also exhibited an association between the A allele and the CLP + CL group (P = 0.0462). These results were confirmed in the probands with European ancestry. CONCLUSIONS: The 8q24 region plays a role in CL/P and the IRF6 G/A haplotype (rs2235371/rs642961) increases the risk for oral cleft in the Brazilian population.
Assuntos
Cromossomos Humanos Par 8 , Fenda Labial/genética , Fissura Palatina/genética , Fatores Reguladores de Interferon/genética , Alelos , População Negra/genética , Brasil , Haplótipos , Humanos , Mutação INDEL , Indígenas Sul-Americanos/genética , Linhagem , Polimorfismo Genético , População Branca/genéticaRESUMO
This study reports on a cytogenetic finding in a bone marrow examination of a 47-year-old male patient treated in the Hematology and Blood Transfusion Service of the Hospital de Base in São José do Rio Preto, São Paulo State, Brazil. The only alteration found at diagnosis of myelodysplastic syndrome (MDS) subtype refractory anemia with excess blasts (RAEB-2) was clonal monosomy of chromosome 21. The patient evolved to acute myeloid leukemia type M2 and died nine months after diagnosis. Clonal monosomy of chromosome 21, as the only cytogenetic abnormality in MDS, has only been reported three times previously. This uncommon cytogenetic abnormality in MDS has been associated with a poor clinical course, although more data will be needed to determine if this prognosis is invariable.
Assuntos
Anemia Refratária com Excesso de Blastos/genética , Leucemia Mieloide Aguda/genética , Anemia Refratária com Excesso de Blastos/diagnóstico , Cromossomos Humanos Par 21/metabolismo , Humanos , Leucemia Mieloide Aguda/diagnóstico , Masculino , Pessoa de Meia-Idade , MonossomiaRESUMO
The aim of the study was to characterize clinically and biochemically mucopolysaccharidosis type II (MPS II) heterozygotes. Fifty-two women at risk to be a carrier, with a mean age of 34.1 years (range 16-57 years), were evaluated through pedigree analysis, medical history, physical examination, measurement of iduronate sulfatase (IDS) activities in plasma and in leukocytes, quantification of glycosaminoglycans (GAGs) in urine, and analysis of the IDS gene. Eligibility criteria for the study also included being 16 years of age or older and being enrolled in a genetic counselling programme. The pedigree and DNA analyses allowed the identification of 40/52 carriers and 12/52 non-carriers. All women evaluated were clinically healthy, and their levels of urinary GAGs were within normal limits. Median plasma and leukocyte IDS activities found among carriers were significantly lower than the values found for non-carriers; there was, however, an overlap between carriers' and non-carriers' values. Our data suggests that MPS II carriers show lower plasma and leukocyte IDS activities but that this reduction is generally associated neither with changes in levels of urinary GAGs nor with the occurrence of clinical manifestations.
Assuntos
Heterozigoto , Mucopolissacaridose II/genética , Adolescente , Adulto , Biomarcadores/análise , Biomarcadores/urina , Estudos de Casos e Controles , Análise Mutacional de DNA , Família , Saúde da Família , Feminino , Glicoproteínas/análise , Glicoproteínas/genética , Glicosaminoglicanos/análise , Glicosaminoglicanos/urina , Humanos , Pessoa de Meia-Idade , Mucopolissacaridose II/diagnóstico , Mucopolissacaridose II/urina , Linhagem , Exame Físico , Adulto JovemRESUMO
This is a case report of macrosomia, obesity, macrocephaly and ocular abnormalities (MOMO syndrome) associated with autism. Studies on genetic or environmental syndromes associated with autism can provide genetic markers or uncover relevant events, and are very important for the definition of autism subgroups in future molecular research.
Assuntos
Anormalidades Múltiplas/genética , Transtorno Autístico/genética , Anormalidades Múltiplas/diagnóstico , Adulto , Anormalidades do Olho/genética , Transtornos do Crescimento/genética , Cabeça/anormalidades , Humanos , Masculino , Transtornos Mentais/genética , Obesidade/genética , SíndromeRESUMO
The molecular pathogenesis of myelodysplastic syndromes (MDS) is poorly understood. In order to expand our knowledge of genetic defects in MDS, we determined the overall profile of genes expressed in bone marrow from patients with refractory anemia with excess blasts (RAEB) by serial analysis of gene expression (SAGE). The present report describes a partial transcriptome of RAEB bone marrow derived from 56,694 sequenced tags that provides information about expressed gene products. This is the first attempt to determine an overall profile of gene expression specifically in RAEB at diagnosis using SAGE, which should be useful in the understanding of the physiopathology of MDS and in identifying the genes involved.
Assuntos
Perfilação da Expressão Gênica/métodos , Expressão Gênica , Síndromes Mielodisplásicas/genética , Adulto , Idoso , Anemia Refratária com Excesso de Blastos/genética , Anemia Refratária com Excesso de Blastos/metabolismo , Medula Óssea/metabolismo , Etiquetas de Sequências Expressas , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Autism spectrum disorders are severe psychiatric diseases commonly identified in the population. They are diagnosed during childhood and the etiology has been much debated due to their variations and complexity. Onset is early and characterized as communication and social interaction disorders and as repetitive and stereotyped behavior. Autistic disorders may occur together with various genetic and chromosomal diseases. Several chromosomal regions and genes are implicated in the predisposition for these diseases, in particular those with products expressed in the central nervous system. There are reports of autistic and mentally handicapped patients with submicroscopic subtelomeric alterations at the distal end of the long arm of chromosome 2. Additionally, there is evidence that alterations at 2q37 cause brain malformations that result in the autistic phenotype. These alterations are very small and not identified by routine cytogenetics to which patients are normally submitted, which may result in an underestimation of the diagnosis. This study aimed at evaluating the 2q37 region in patients with autistic disorders. Twenty patients were studied utilizing the fluorescence in situ hybridization technique with a specific probe for 2q37. All of them were also studied by the GTC banding technique to identify possible chromosomal diseases. No alterations were observed in the 2q37 region of the individuals studied, and no patient presented chromosomal diseases. This result may be due to the small sample size analyzed. The introduction of routine analysis of the 2q37 region for patients with autistic disorders depends on further studies.
Assuntos
Transtorno Autístico/genética , Cromossomos Humanos Par 2/genética , Criança , Transtornos Globais do Desenvolvimento Infantil/genética , Aberrações Cromossômicas , Cromossomos Humanos Par 2/ultraestrutura , Análise Citogenética , Predisposição Genética para Doença , Humanos , Hibridização in Situ Fluorescente , Metáfase/genética , Telômero/genéticaRESUMO
Investigation of the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in chronic myeloid leukemia patients is essential to predict prognosis and survival. In 20 patients treated at the Bone Marrow Transplantation Unit of São José do Rio Preto (São Paulo, Brazil), we used fluorescence in situ hybridization (FISH) to investigate the frequency of cells with BCR/ABL rearrangement at diagnosis and at distinct intervals after allo-HSCT until complete cytogenetic remission (CCR). We investigated the disease-free survival, overall survival in 3 years and transplant-related mortality rates, too. Bone marrow samples were collected at 1, 2, 3, 4, 6, 12, and 24 months after transplantation and additional intervals as necessary. Success rate of the FISH analyses was 100%. CCR was achieved in 75% of the patients, within on average of 3.9 months; 45% patients showed CCR within 60 days after HSCT. After 3 years of the allo-HSCT, overall survival rate was 60%, disease-free survival was 50% and the transplant-related mortality rate was 40%. The study demonstrated that the BCR-ABL FISH assay is useful for follow-up of chronic myeloid leukemia patients after HSCT and that the clinical outcome parameters in our patient cohort were similar to those described for other bone marrow transplantation units.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Hibridização in Situ Fluorescente/métodos , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/cirurgia , Adolescente , Adulto , Transplante de Medula Óssea , Brasil , Intervalo Livre de Doença , Departamentos Hospitalares , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Transplante Homólogo , Resultado do TratamentoRESUMO
Autism spectrum disorders are severe psychiatric diseases commonly identified in the population. They are diagnosed during childhood and the etiology has been much debated due to their variations and complexity. Onset is early and characterized as communication and social interaction disorders and as repetitive and stereotyped behavior. Austistic disorders may occur together with various genetic and chromosomal diseases. Several chromosomal regions and genes are implicated in the predisposition for these diseases, in particular those with products expressed in the central nervous system. There are reports of autistic and mentally handicapped patients with submicroscopic subtelomeric alterations at the distal end of the long arm of chromosome 2. Additionally, there is evidence that alterations at 2q37 cause brain malformations that result in the autistic phenotype. These alterations are very small and not identified by routine cytogenetics to which patients are normally submitted, which may result in an underestimation of the diagnosis. This study aimed at evaluating the 2q37 region in patients with autistic disorders. Twenty patients were studied utilizing the fluorescence in situ hybridization technique with a specific probe for 2q37. All of them were also studied by the GTC banding technique to identify possible chromosomal diseases. No alterations were observed in the 2q37 region of the individuals studied, and no patient presented chromosomal diseases. This result may be due to the small sample size analyzed. The introduction of routine analysis of the 2q37 region for patients with autistic disorders depends on further studies.
Assuntos
Humanos , Masculino , Feminino , Criança , /genética , Transtorno Autístico/genética , Aberrações Cromossômicas , Análise Citogenética , /ultraestrutura , Predisposição Genética para Doença , Hibridização in Situ Fluorescente , Metáfase , Telomerase/genética , Transtornos Globais do Desenvolvimento Infantil/genéticaRESUMO
Investigation of the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in chronic myeloid leukemia patients is essential to predict prognosis and survival. In 20 patients treated at the Bone Marrow Transplantation Unit of São José do Rio Preto (São Paulo, Brazil), we used fluorescence in situ hybridization (FISH) to investigate the frequency of cells with BCR/ABL rearrangement at diagnosis and at distinct intervals after allo-HSCT until complete cytogenetic remission (CCR). We investigated the disease-free survival, overall survival in 3 years and transplant-related mortality rates, too. Bone marrow samples were collected at 1, 2, 3, 4, 6, 12, and 24 months after transplantation and additional intervals as necessary. Success rate of the FISH analyses was 100%. CCR was achieved in 75% of the patients, within on average of 3.9 months; 45% patients showed CCR within 60 days after HSCT. After 3 years of the allo-HSCT, overall survival rate was 60%, disease-free survival was 50% and the transplant-related mortality rate was 40%. The study demonstrated that the BCR-ABL FISH assay is useful for follow-up of chronic myeloid leukemia patients after HSCT and that the clinical outcome parameters in our patient cohort were similar to those described for other bone marrow transplantation units.
Assuntos
Humanos , Adolescente , Adulto , Pessoa de Meia-Idade , Hibridização in Situ Fluorescente/métodos , Leucemia Mielogênica Crônica BCR-ABL Positiva/cirurgia , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Medula Óssea , Brasil , Departamentos Hospitalares , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Prognóstico , Taxa de Sobrevida , Intervalo Livre de Doença , Transplante Homólogo , Resultado do TratamentoRESUMO
The present report describes the karyotypic findings in cells from a Wilms' tumor. The most consistent cytogenetic abnormalities detected consisted of translocations involving break and fusion of chromosomal telomeres and telomeric associations frequently affecting the terminus of the short arms of chromosomes 14 and 17.
Assuntos
Aberrações Cromossômicas , Neoplasias Renais/genética , Telômero/ultraestrutura , Translocação Genética , Tumor de Wilms/genética , Pré-Escolar , Bandeamento Cromossômico , Cromossomos Humanos Par 14 , Cromossomos Humanos Par 17 , Humanos , Cariotipagem , Neoplasias Renais/patologia , Masculino , Tumor de Wilms/patologiaRESUMO
O presente trabalho descreve uma paciente portadora de câncer de pulmäo que apresenta material heterocromático extra no braço curto do cromossomo 15. A análise em bandamento G, C, Q é Ag-NOR sugere uma translocaçäo envolvendo o braço do cromossomo T e o braço curto do cromossomo 15
Assuntos
Humanos , Feminino , Cromossomos Humanos Par 15 , Neoplasias Pulmonares/genética , Translocação Genética , Cromossomo YRESUMO
We report on 4 new patients with acheiropodia ("the handless and footless families of Brazil"). This autosomal recessive condition involves all 4 limbs with a well-defined pattern of defects. Two of the patients described here had a small bone fragment in the upper stumps (Bohomoletz bone), an uncommon finding in acheiropodia.
Assuntos
Deformidades Congênitas do Pé , Deformidades Congênitas da Mão , Brasil , Criança , Pré-Escolar , Feminino , Deformidades Congênitas do Pé/genética , Deformidades Congênitas da Mão/genética , Humanos , Lactente , Masculino , LinhagemRESUMO
Bloom's syndrome (BS) is an autosomal recessive disease characterized by short stature, sensitivity to sunlight, and telangiectasic malar erythema. It is associated to chromosomal breakage, to primary combined immunodeficiency, and to a high incidence of neoplasias. The authors report the case of two siblings with BS and associated immunodeficiency. Both patients were male and 5 (A) and 4 (B) years old at the time of diagnosis. Chronic diarrhea, recurrent otitis media, purulent rhinitis, conjunctivitis and pyodermatitis were reported by patient A. Patient B was admitted with diagnosis of bilateral neuroblastoma and had the tumor resected. Later on, he presented with oral moniliasis, herpetic stomatitis, and skin abscesses. This patient did not have recurrent infections. Immunological evaluation showed normal serum levels of CH50, C3, and C4 for both patients. Serum IgG, IgA, IgM, and salivary IgA levels were: 455 mg/dl, 15mg/dl, 20mg/dl, 0.6mg/dl for A, and 400mg/dl, 15mg/dl, 20mg/dl, and 0.2mg/dl for B, respectively. Serum antipolio antibodies (1, 2, and 3) were normal, and low levels of isohemagglutinins were observed in both patients. T cells subset determination showed: patient A--OKT3 = 66%, OKT4 = 33%, OKT8 = 32%, and 4/8 ratio = 1.0; patient B--OKT3 = 70%, OKT4 = 32%, OKT8 = 34%, and 4/8 ratio = 1.0. In vitro cellular immune response to PHA was depressed only in patient B. Patients karyotype showed chromosomal breaks with sister chromatid exchanges. Neither patient had abnormal alphafetoprotein and carcinoembryonic antigen serum levels. The rarity of such associations justifies the presentation of the cases.