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- ItemSomente MetadadadosActivation of the Janus kinase/signal transducer and activator of transcription pathway in multiple myeloma is not related to point mutations in kinase and pseudokinase domains of JAK1(Informa Healthcare, 2014-05-01) Corbi, Fernanda Cristina [UNIFESP]; Oliveira, Mariana Bleker de [UNIFESP]; Morelli, Vania M. [UNIFESP]; Han, Sang W. [UNIFESP]; Renauld, Jean-Christophe; Knoops, Laurent; Colleoni, Gisele Wally Braga [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Ludwig Inst Canc Res; Catholic Univ Louvain; Clin Univ St LucConsidering the recent impact of tyrosine kinase inhibitors in the treatment of myeloproliferative disorders carrying a recurrent JAK2 mutation not identified in multiple myeloma (MM), this study aimed to search for mutations in kinase and pseudokinase domains of the JAK1 gene in an attempt to define any critical and recurring change that can be used as a therapeutic target. We obtained CD138 + purified cells from 27 bone marrow aspirates of untreated MM, four normal controls and four MM cell lines. After amplification of kinase and pseudokinase domains of JAK1 in cDNA samples, the fragments were automatically sequenced. Seventy-eight percent of MM cases showed at least one polymorphism, all being synonymous single nucleotide polymorphisms (SNPs), with allele frequencies consistent with previous studies in normal European, African American and Asian populations. the four cell lines also showed only synonymous SNPs. Mutations in the kinase and pseudokinase domains of the JAK1 gene do not seem to be important for activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway because we were not able to find any recurrent mutation in a case series of 27 patients and four MM cell lines.
- ItemSomente MetadadadosBladder Dysfunction in a New Mutant Mouse Model With Increased Superoxide-Lack of Nitric Oxide?(Elsevier B.V., 2010-02-01) Soler, Roberto [UNIFESP]; Fuellhase, Claudius; Lu, Baisong; Bishop, Colin E.; Andersson, Karl-Erik; Wake Forest Univ; Universidade Federal de São Paulo (UNIFESP); Univ MunichPurpose: Nitric oxide mediates urethral smooth muscle relaxation and may also be involved in detrusor activity control. Mice with mutation in the Immp2l gene have high superoxide ion levels and a consequent decrease in the bioavailable amount of nitric oxide. We studied bladder function in this mouse model.Material and Methods: Young male mutants at ages 4 to 6 months, old female mutants at age 18 months and healthy WT age matched controls were used. the detrusor contractile response to carbachol and electrical field stimulation was tested in isolated detrusor strips in organ baths. in vivo bladder function was evaluated by cystometry in conscious animals.Results: Young male mutants had significantly lower micturition and higher post-void residual volume than WT controls. They had pronounced voiding difficulty and strained when initiating micturition. Detrusor contractile responses to carbachol and electrical field stimulation were similar in mutant and WT mice. Old female mutant mice had lower bladder capacity and micturition volume, and higher micturition frequency and bladder-to-body weight ratio than WT controls. in the in vitro study detrusor strips from mutants showed a lower maximum response to carbachol.Conclusions: Mice with mutation in the Immp2l gene have bladder dysfunction, mainly characterized by emptying abnormalities in young males and increased detrusor activity in old females. Detrusor function was preserved in young males and impaired in old females. These animals are a natural model of oxidative stress with low bioavailable nitric oxide. Thus, they are interesting tools in which to evaluate the role of these conditions on bladder dysfunction.
- ItemAcesso aberto (Open Access)Caracterização clínica, molecular e imunológica de pacientes com síndrome poliglandular autoimune do tipo 1(Universidade Federal de São Paulo (UNIFESP), 2016-01-27) Weiler, Fernanda Guimarães [UNIFESP]; Castro, Marise Lazaretti [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Introduction: Autoimmune polyendocrine syndrome type 1 (APS1) is an autosomal recessive disorder defined by the association of at least two of the three major diseases: chronic mucocutaneous candidiasis (CMC), hypoparathyroidism, and autoimmune adrenal insufficiency, however, many other autoimmune components may develop. In most cases, APS1 appears in infancy or childhood. The disease is caused by mutations in the AIRE gene, resulting in defective AIRE protein, which is essential for self-tolerance through thymic expression of peripheral self-proteins, and deletion of autoreactive T cells. In Brazil, however, the characteristics of APS1 patients are still unknown. Objective: To define the clinical profile of Brazilian APS1 patients; to perform mutational analysis of AIRE gene; to investigate genotype/phenotype correlations; to perform functional study of a novel mutation; and to measure specific autoantibodies. Patients and methods: Information about clinical history was evaluated by a questionnaire, and antibodies against interferon type I and interleukins 17A, 17F and 22 were measured in the sera of the patients. Genomic DNA was used to perform sequencing of all 14 exons and exon/intron boundaries of the AIRE gene. For localization analysis by immunofluorescence microscopy, HeLa cells were transfected with wild-type and mutant (c.560C>G) plasmids. Results: Thirteen patients with clinical diagnosis of APS1 were identified and in all cases the disease first appeared during infancy or childhood. Twenty different manifestations have been diagnosed. Besides being the first sign in the majority (77%), CMC was also the most frequent manifestation, present in all patients. Hypoparathyroidism was observed in 69% and adrenal insufficiency was diagnosed in 77%, while the complete triad was present in 54% of the sample. Every patient carried defects in AIRE, and among 10 identified mutations, 4 have never been reported (c.560C>G, c.966C>A, c.1096-2A>G and c.1347C>A). The most frequent mutation was the c.967_979del, which accounted for 36% of the alleles. As in other series, we were unable to identify correlations between phenotype and the detected mutations. Mutational analyses of relatives allowed the identification of APS1 in an asymptomatic child. In transiently transfected cells, the mutant c.560C>G protein was observed as abnormal perinuclear aggregates, which suggested the mutation harmful potential. All 10 confirmed APS1 patients that were tested for anti-interferon type I showed positive results, and we have found that anti-interleukin-17A titers were negatively correlated with number of manifestations in each patient. Thirteen patients suspected of having the syndrome were also investigated; one of them displayed another new mutation of AIRE, which is expected to be deleterious according to in silico simulations. Conclusions: We were able to identify 14 Brazilian patients with APS1, one of them still asymptomatic. In our cohort, CMC was the most prevalent disease, while the most common mutation was c.967_979del. We detected 4 novel mutations, and another mutation likely to be deleterious in a patient suspected of having the syndrome was also reported. Titers of anti-interleukin-17A were negatively correlated with number of manifestations. Screening for AIRE mutations and analysis of specific auto-antibodies are useful tools to establish the diagnosis in initial or atypical situations.
- ItemSomente MetadadadosCarcinoma medular da tireoide e feocromocitoma esporádico e hereditário: investigação de eventos genéticos somáticos no gene ret(Universidade Federal de São Paulo (UNIFESP), 2014-12-18) Bim, Larissa Valdemarin [UNIFESP]; Cerutti, Janete Maria Cerutti [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Introduction: Mutations in the RET gene are associated with MEN 2 syndrome (multiple endocrine neoplasia type 2), which includes three types: familial medullary carcinoma (FMTC), characterized by medullary thyroid carcinoma (MTC) alone; MEN 2A, characterized by CMT associated with pheochromocytoma (OEMs) and hyperparathyroidism, and NOT 2B. Our group described a novel mutation (G533C) in exon 8 of RET gene in a family with MEN 2A. Although RET is responsible for hereditary predisposition to the development of endocrine tumors associated with this syndrome has been suggested that additional somatic mutations are required for tumor development and progression. In an individual of this family diagnosed with OEMs, we investigated the presence of somatic mutations in the RET gene and two new variants (G548V and S556T) were found. Objective: To investigate the prevalence of these new variants and seek new somatic genetic events associated with the OEM and CMT. Materials and Methods: Genomic DNA was extracted for PCR amplification and Sanger sequencing performed FeO (n = 23) MTC (n = 40), other tumors (n = 15) and paired peripheral blood (n = 27). Results: identified a new genetic event in the RET gene associated with the genesis of the CMT and OEMs who was absent in peripheral blood and other tumor types. Studies in silico (1000 genome analysis) found no previous reports of this event in the genome of normal individuals. The G548V mutation is associated with the event (47.9% and 27.5% Feo CMT) in homo- and heterozygous but not parental gene. Conclusion: We describe for the first time a possible event in the RET gene, somatic origin in tumors associated with MEN 2. Other groups reported other somatic changes in tumors related to MEN 2, strengthening the hypothesis of additional mutations and our data. However, other studies are necessary to confirm the presence of this event in somatic and its location in the genome.
- ItemSomente MetadadadosThe frequency of 844ins68 mutation in the cystathionine beta-synthase gene is not increased in patients with venous thrombosis(Ferrata Storti Foundation, 1998-11-01) Franco, Rendrik; Maffei, Francisco Humberto de Abreu [UNIFESP]; Lourenco, Dayse Maria [UNIFESP]; Piccinato, Carlos; Morelli, Vania Maris [UNIFESP]; Thomazini, Isolete; Zago, Marco; Universidade de São Paulo (USP); FUNDHERP; Universidade Federal de São Paulo (UNIFESP)Background and Objectives. A frequent mutation in the cystathionine beta-synthase (CBS) gene (844ins68, a 68-bp insertion in the coding region of exon 8) was recently discovered. In the present study we Investigated this mutation as a candidate risk factor for venous thrombosis.Design and Methods. The prevalence of the 844ins68 CBS mutation was determined in 101 patients with objectively diagnosed deep venous thrombosis and in 101 healthy controls matched for age, sex and race. PCR amplification of a DNA fragment containing exon 8 of the CBS gene was employed to determine the genotypes, Additionally, Bsrl restriction enzyme digestion of the PCR products was performed in all samples from carriers of the insertion, to test for concurrent presence of a second mutation (T833C) in the CBS gene.Results. The insertion was found in 21 out of 101 patients (20.8%; allele frequency 0.109) and in 20 out of 101 controls (19.8%; allele frequency 0.114), yielding a relative risk for venous thrombosis related to the 844ins68 CBS mutation close to 1.0. In addition, the T833C GBS mutation was detected in all alleles carrying the 844ins68 CBS insertion, confirming the co-inheritance of the two mutations.Interpretation and Conclusions. Our findings do not support the hypothesis that the 844ins68 mutation in the CBS gene is a genetic risk factor for venous thrombosis. (C)1998, Ferrata Storti Foundation.
- ItemAcesso aberto (Open Access)Homozygotic intronic GAA mutation in three siblings with late-onset Pompe's disease(Academia Brasileira de Neurologia - ABNEURO, 2010-04-01) Grzesiuk, Anderson Kuntz; Shinjo, Sueli Mieko Oba; Silva, Roseli da; Machado, Marcela [UNIFESP]; Galera, Marcial Francis [UNIFESP]; Marie, Suely Kazue Nagahashi; INEC Hospital Santa Rosa; University of São Paulo School of Medicine Department of Neurology; Universidade Federal de São Paulo (UNIFESP); University of Cuiabá School of MedicinePompe's disease (PD) is a metabolic myopathy caused by the accumulation of lysosomal glycogen, secondary to acid α-glucosidase (GAA) enzyme deficiency. Childhood and late-onset forms are described, differing by the age of onset and symptoms. In this study were analyzed affected siblings with Pompe's disease (PD) and their distinct clinical and pathological presentations. METHOD: Diagnosis was performed by the clinical presentation of limb-girdle dystrophies and respiratory compromise. Confirmatory diagnoses were conducted by muscle biopsy, GAA activity measurement and by GAA gene genotyping. RESULTS: The findings suggested muscular involvement due to GAA deficiency. GAA genotyping showed they are homozygous for the c.-32-3C>A mutation. CONCLUSION: Herein we reported a family where three out of five siblings were diagnosed with late-onset PD, although it is a rare metabolic disease inherited in an autossomal recessive manner. We emphasize the importance of including this presentation within the differential diagnoses of the limb-girdle dystrophies once enzyme replacement therapy is available.
- ItemAcesso aberto (Open Access)Interação entre audiologia e genética no estudo de uma família: a complexidade do diagnóstico molecular e do aconselhamento genético(ABORL-CCF Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial, 2008-10-01) Hoffmann, Flavia Maria Rodrigues; Rodrigues, Patrícia Fernandes [UNIFESP]; Santos, Teresa Maria Momensohn dos [UNIFESP]; Sartorato, Edi Lucia; Maciel-guerra, Andréa Trevas; Matas, Carla Gentile [UNIFESP]; Moraes, Vanessa Cristine Sousa de; Instituto de Estudos Avançados da Audição; Universidade Federal de São Paulo (UNIFESP); Instituto de Estudos da Audição; Universidade Estadual de Campinas (UNICAMP); Universidade de São Paulo (USP); FAPESPHearing loss is a multifaceted condition with many etiologies, among which genetic mutation is. Therefore, it is important to connect audiological investigation to etiological diagnosis. AIM: this study aims to establish the audiological and genetic profiles of three non-syndromic children with sensorineural hearing loss. MATERIALS AND METHOD: three brothers aged 3, 5 and 16 were enrolled in this study. They were submitted to behavioral and electrophysiological hearing tests and molecular studies. RESULTS: the hearing tests showed moderate to moderately severe bilateral symmetric sensorineural hearing loss and an accentuated descending slope. Transient and Distortion Product Otoacoustic emissions were absent in the two younger children. ABR showed a bilateral moderately severe to severe sensorineural hearing loss. P300 showed bilateral normal latencies in the older brother. Molecular tests showed that the two younger children were heterozygote for mutation 35delG on gene GJB2. CONCLUSION: The combination of speech and hearing tests and genetic analysis allows for the etiologic diagnosis of seemingly similar hearing loss cases, which however display different genetic backgrounds. Molecular studies must be comprehensive enough to avoid precipitated diagnosis which may impair genetic counseling.
- ItemSomente MetadadadosMini-Mu insertions in the tetracycline resistance determinant from Proteus mirabilis(Assoc Bras Divulg Cientifica, 1997-03-01) Magalhaes, Vanda Dolabela de [UNIFESP]; Castilho, Beatriz Amaral de [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)The inducible tetracycline resistance determinant isolated from Proteus mirabilis cloned into the plasmid pACYC177 was mutagenized by insertion of a mini-Mu-lac phage in order to define the regions in the cloned sequences encoding the structural and regulatory proteins. Three different types of mutants were obtained: one lost the resistance phenotype and became Lac(+); another expressed the resistance at lower levels and constitutively; the third was still dependent on induction but showed a lower minimal inhibitory concentration. The mutant phenotypes and the locations of the insertions indicate that the determinant is composed of a repressor gene and a structural gene which are not transcribed divergently as are other known tetracycline determinants isolated from Gram-negative bacteria.
- ItemAcesso aberto (Open Access)Molecular characterization of hepatitis C virus in end-stage renal disease patients under hemodialysis(Wiley, 2018) da Silva, Rafael Alves [UNIFESP]; Todao, Jardelina de Souza [UNIFESP]; Kamitani, Fernando Luiz; Benedito Silva, Antonio Eduardo [UNIFESP]; de Carvalho-Filho, Roberto Jose [UNIFESP]; Cardoso Gomes Ferraz, Maria Lucia [UNIFESP]; Vicente Guedes de Carvalho, Isabel Maria [UNIFESP]New direct-acting antiviral (DAA) agents are in development or already approved for the treatment of chronic hepatitis C virus (HCV) infection. The effectiveness of these drugs is related to the previous existence of resistant variants. Certain clinical conditions can allow changes in immunological characteristics of the host and even modify genetic features of viral populations. The aim of this study was to perform HCV molecular characterization from samples of end-stage renal disease patients on hemodialysis (ESRD-HD). Nested PCR and Sanger sequencing were used to obtain genetic information from the NS5B partial region of a cohort composed by 86 treatment-naive patients. Genomic sequences from the Los Alamos databank were employed for comparative analysis. Bioinformatics methodologies such as phylogenetic reconstructions, informational entropy, and mutation analysis were used to analyze datasets separated by geographical location, HCV genotype, and renal function status. ESRD-HD patients presented HCV genotypes 1a (n=18), 1b (n=16), 2a (n=2), 2b (n=2), and 3a (n=4). Control subjects were infected with genotypes 1a (n=11), 1b (n=21), 2b (n=4), and 3a (n=8). Dataset phylogenetic reconstruction separated HCV subtype 1a into two distinct clades. The entropy analysis from the ESRD-HD group revealed two amino acid positions related to an epitope for cytotoxic T lymphocytes and T helper cells. Genotype 1a was found to be more diverse than subtype 1b. Also, genotype 1a ERSD-HD patients had a higher mean of amino acids changes in comparison to control group patients. The identification of specific mutations on epitopes and high genetic diversity within the NS5B HCV partial protein in hemodialysis patients can relate to host immunological features and geographical distribution patterns. This genetic diversity can affect directly the new DAA's resistance mechanisms.
- ItemSomente MetadadadosN-RAS and K-RAS gene mutations in Brazilian patients with multiple myeloma(Taylor & Francis Ltd, 2006-02-01) Ortega, Manoela M.; Faria, Rosa MD [UNIFESP]; Shitara, Edson S.; Assis, Angela M.; Albuquerque, Dulcinéia M.; Oliveira, José SR; Noguti, Maria Aparecida Eiko [UNIFESP]; Faria, Jose Roberto de [UNIFESP]; Costa, Fernando Ferreira [UNIFESP]; Lima, Carmen Silvia Passos; Universidade Estadual de Campinas (UNICAMP); Universidade Federal de São Paulo (UNIFESP)Point mutations affecting codons 12, 13 (exon 1) and 61 (exon 2) of the N-RAS gene and codons 12 and 13 (exon 1) of the K-RAS gene are identified in approximately 30.0% and 10.0%, respectively, of multiple myeloma (MM) patients living in the northern hemisphere. To date, there are no reports about the prevalence of RAS gene mutations in MM Brazilian patients, and this comprised the aim of the present study. DNA from bone marrow aspirates of 252 patients with MM (139 males and 113 females; aged 59.33 +/- 11.95 years) were investigated for whole exons 1 and 2 of the N-RAS gene and whole exon 1 of the K-RAS gene by direct sequencing of DNA amplified in vitro by the polymerase chain reaction. Fifty-three out of 252 (21.03%) MM patients presented RAS mutations. Heterozygous mutations at codons 4, 10 (exon 1), 61 and 65 (exon 2) of the N - RAS gene were identified in seven out of 252 (2.78%) patients. K-RAS heterozygous mutations at codons 7, 12, 13 (exon 1) were seen in 46 out of 252 (18.25%) patients. To the best of our knowledge, the mutation at codon 7 of K-RAS gene is reported for the first time in MM. Taken together, these results suggest that Brazilian MM patients are characterized by: (i) a low prevalence of RAS mutation and (ii) RAS mutations located at distinct regions of the critical codons of the N - RAS and K-RAS genes.
- ItemAcesso aberto (Open Access)Neoplasias mieloproliferativas: revisão dos critérios diagnósticos e dos aspectos clínicos(Associação Brasileira de Hematologia e Hemoterapia e Terapia Celular, 2010-01-01) Chauffaille, Maria de Lourdes Lopes Ferrari [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Chronic myeloproliferative disorders, currently called myeloproliferative neoplasms (MPN), according to the 4th edition of the World Health Organization (WHO) classification are clonal diseases of hematopoietic stem cells, in which there is increased proliferation of the myeloid series (granulocytic, erythrocytic, megakaryocytic series or mast cells) with effective maturation. The progression of all is characterized by marrow fibrosis or leukemic transformation. According to the WHO classification, the MPNs include: chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), idiopathic myelofibrosis (IM), chronic neutrophilic leukemia (CNL), chronic eosinophilic leukemia not otherwise categorized (CEL-NC), mastocytosis (M) and myeloproliferative neoplasm unclassifiable (MPNU). It is worth noting that the molecular basis of CML (BCR/ABL1), as well as PV,ET, IM (JAK2V617F and exon 12, MPL W515L/K) and M (KITD816V) have been identified and have, in common, constitutive activation of tyrosine kinase due to acquired hematopoietic stem cell defects. The JAK2V617F mutation is observed in around 90% of PV cases and in around 50-60% of IM and ET leading to the question why a single molecular lesion induces three different clinical manifestations. There is already evidence that additional genetic and epigenetic events contribute to the pathogenesis, including MPL W515L/K mutation. Some clinical aspects, the pathophysiology and diagnostic criteria of MPNs are presented in this paper.
- ItemSomente MetadadadosThe Novel WT1 Gene Mutation p.H377N Associated to Denys-Drash Syndrome(Lippincott Williams & Wilkins, 2010-08-01) Guaragna, Mara Sanches; Soardi, Fernanda Caroline; Assumpcao, Juliana Godoy; Zambaldi, Lilian de Jesus Girotto; Cardinalli, Izilda Aparecida; Yunes, Jose Andres; Mello, Maricilda Palandi de [UNIFESP]; Brandalise, Silvia Regina; Aguiar, Simone dos Santos; Ctr Infantil Boldrini; Universidade Estadual de Campinas (UNICAMP); Universidade Federal de São Paulo (UNIFESP)Denys-Drash syndrome (DDS, Online Mendelian Inheritance in Man number 194080) is a rare human developmental disease generally occurring in 46,XY individuals characterized by the combination of disorder of sex development, early onset nephropathy, and Wilms' tumor (WT). DDS is mainly caused by mutations in the WT1 gene. This report describes a novel WT1 gene mutation in a DDS patient. Sequencing the WT1 gene revealed a heterozygous transversion CAT > AAT within exon 8, causing the substitution of an asparagine for a histidine at residue 377. the p.H377N mutation is predicted to diminish the WT1 protein DNA-binding affinity as it might disrupt the normal zinc finger 2 conformation.
- ItemSomente MetadadadosSearch for mutations in signaling pathways in head and neck squamous cell carcinoma(Spandidos Publ Ltd, 2013-07-01) Carvalho, Thais Gulim de [UNIFESP]; Carvalho, Ana Carolina de [UNIFESP]; Maia, Danielle Calheiros Campelo [UNIFESP]; Ogawa, Juliana Kaori [UNIFESP]; Carvalho, Andre Lopes; Vettore, Andre Luiz [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Barretos Canc HospMutations in JAK-STAT signaling pathway genes have been associated with the development of various hematological tumors, but have not been investigated in head and neck tumors, and the PIK3CA, BRAF and KRAS genes have been described in a few cases of head and neck squamous cell carcinoma (HNSCC). in the present study, we determined the mutation status in members of the MAPK, PI3K-AKT and JAK-STAT pathways in HNSCC. Mutations in the KRAS, BRAF, PIK3CA, JAK1 and JAK2 genes were evaluated in 94 HNSCCs by direct DNA sequencing analysis using cDNA synthesized from RNA extracted from patient tumor cells. All patients evaluated had wild-type KRAS, BRAF and PIK3CA genes. Furthermore, although some known polymorphisms have been found in JAK1 genes (rs45598436, rs17127063, rs2230587, rs3737139, rs2230588 and rs12129819) and JAK2 (rs10429491, rs2230723, rs2230724 and rs41316003), no mutation could be detected. Our data indicate that mutations in these kinase genes seem to be rare events in HNSCC.
- ItemSomente MetadadadosTGFBI gene mutations in Brazilian patients with corneal dystrophy(Nature Publishing Group, 2007-05-01) Solari, H. P.; Ventura, M. P.; Perez, A. B. A.; Sallum, J. M. R.; Burnier, M. N.; Belfort, Rubens Junior [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); McGill UnivPurpose To investigate the transforming growth factor beta-induced gene ( TGFBI) mutations in Brazilian patients with corneal dystrophy and to evaluate the phenotype genotype correlation in these patients.Methods A total of 11 unrelated families were studied. the diagnosis of corneal dystrophy was based on clinical and histopathological findings. Genomic DNA was extracted from peripheral blood leucocytes, and exons 4 and 12 of the TGFBI gene were amplified by polymerase chain reaction followed by direct sequencing on both strands.Results Five different mutations in the TGFBI gene were found in the probands. We identified the following mutations: lattice corneal dystrophy - R124C and A546T; Reis-Bucklers corneal dystrophy - R555Q and R124L; granular corneal dystrophy - R555W and Avellino dystrophy - R555W. in three of the 11 studied families there was no mutation in exons 4 and 12.Conclusions This is the first report of mutations in the TGFBI gene in a series of Brazilian patients with corneal dystrophy. the findings indicate that TGFBI gene screening should be considered in the diagnosis of corneal dystrophy.