RESUMO
We compared the effects of continuous exercise (CE) vs accumulated exercise (AE) training on CVD risk factors and heart of young male Wistar rats. The exercise training (ET) was performed in a swimming pool for 30-60 min/day, 5 days/week over 15 weeks. CE group performed the ET in a single long daily session (30-60 min), while AE group performed the ET at the same frequency, intensity, and duration of CE rats, but in three short bouts over the course of a day (10-20 min in three daily sessions). AE training was more efficient than CE in attenuating body and fat weight gain and inhibiting visceral adipocyte hypertrophy at the same food intake level. CE training was more efficient in improving systolic blood pressure, LDL/HDL cholesterol, and serum triglyceride. Both ET protocols increased heart function, decreased lipid peroxidation, and increased intracellular Hsp72 content in the heart. This work shows distinct beneficial effects of CE vs AE training suggesting that the prescription of one or other may be preferred to prevent the increase of a specific CVD risk factor.
Assuntos
Doenças Cardiovasculares/prevenção & controle , Coração/fisiologia , Condicionamento Físico Animal/métodos , Animais , Pressão Sanguínea , Proteínas de Choque Térmico HSP72/metabolismo , Gordura Intra-Abdominal , Lipídeos/sangue , Masculino , Ratos Wistar , Fatores de Risco , Aumento de PesoRESUMO
Although bodypainting has been reported as a great resource for teaching surface anatomy of humans, its use in veterinary anatomy has not been scientifically reported. In the present study, bodypainting was performed on 4 horses for anatomy teaching purposes of the equine locomotor apparatus. We aimed to use the bodypainting method as an additional tool to classic teaching and to test the relevance of our purpose. Twenty one Brazilian veterinary students were given a 90-min session, which included a presentation of painted horses, with opportunities for the students to ask questions and to palpate anatomic locations on the horses. Based on a questionnaire, there was unanimous student satisfaction with this technique. Furthermore, student scores on practical tests to evaluate the attention retain given immediately before and 1 h after the session were 33.9 ± 19.8% and 69.0 ± 18.4%, respectively (p < 0.001). We concluded that bodypainting has great potential for support the classic lectures of the equine locomotor apparatus.
RESUMO
BACKGROUND: Recent studies indicate an increased frequency of mutations in the gene encoding glucocerebrosidase (GBA), a deficiency of which causes Gaucher's disease, among patients with Parkinson's disease. We aimed to ascertain the frequency of GBA mutations in an ethnically diverse group of patients with Parkinson's disease. METHODS: Sixteen centers participated in our international, collaborative study: five from the Americas, six from Europe, two from Israel, and three from Asia. Each center genotyped a standard DNA panel to permit comparison of the genotyping results across centers. Genotypes and phenotypic data from a total of 5691 patients with Parkinson's disease (780 Ashkenazi Jews) and 4898 controls (387 Ashkenazi Jews) were analyzed, with multivariate logistic-regression models and the Mantel-Haenszel procedure used to estimate odds ratios across centers. RESULTS: All 16 centers could detect two GBA mutations, L444P and N370S. Among Ashkenazi Jewish subjects, either mutation was found in 15% of patients and 3% of controls, and among non-Ashkenazi Jewish subjects, either mutation was found in 3% of patients and less than 1% of controls. GBA was fully sequenced for 1883 non-Ashkenazi Jewish patients, and mutations were identified in 7%, showing that limited mutation screening can miss half the mutant alleles. The odds ratio for any GBA mutation in patients versus controls was 5.43 across centers. As compared with patients who did not carry a GBA mutation, those with a GBA mutation presented earlier with the disease, were more likely to have affected relatives, and were more likely to have atypical clinical manifestations. CONCLUSIONS: Data collected from 16 centers demonstrate that there is a strong association between GBA mutations and Parkinson's disease.
Assuntos
Glucosilceramidase/genética , Mutação , Doença de Parkinson/genética , Idoso , Estudos de Casos e Controles , Genótipo , Humanos , Judeus/genética , Modelos Logísticos , Pessoa de Meia-Idade , Análise Multivariada , Razão de ChancesRESUMO
The objective of this study was to evaluate and correlate quality of life (QoL), and stimulus perception of complete denture users, before and after the insertion of new prostheses. We selected 60 patients using bimaxillary complete conventional dentures who needed to replace their prostheses. During anamnesis, we collected demographic data and applied the Oral Health Impact Profile for Edentulous Patients (OHIP-EDENT) questionnaire and stimulus perception questionnaire (PERCEPTION). Before installation of new prostheses, the patients responded to OHIP-EDENT questionnaire, and on the day of installation, they responded to PERCEPTION questionnaire. At the patients' 3-month follow-up, we re-administered the OHIP-EDENT and PERCEPTION questionnaires. The Wilcoxon and MacNemar tests were used to compare patient responses between the time points analysed. Most of the OHIP-EDENT items showed a highly significant impact of the new prostheses on oral health (P ≤ 0·003). The PERCEPTION questionnaire data indicated that the patients experienced significant improvements (P < 0·05) in terms of their sensations with the new prostheses. Cross-lagged data analysis did not show any causality between the OHIP-EDENT and PERCEPTION questionnaires (ZPF test, P = 0·772). We concluded that the treatment was effective with respect to the patients' QoL and their adaptation to the new prostheses.
Assuntos
Prótese Total/psicologia , Boca Edêntula/reabilitação , Satisfação do Paciente , Percepção , Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Inquéritos de Saúde Bucal , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Boca Edêntula/psicologia , Saúde Bucal , Inquéritos e Questionários , Resultado do TratamentoRESUMO
Sampling protocols for detecting Salmonella on poultry differ among various countries. In the United States, the U.S. Department of Agriculture Food Safety and Inspection Service dictates that whole broiler carcasses should be rinsed with 400 ml of 1% buffered peptone water, whereas in the European Union 25-g samples composed of neck skin from three carcasses are evaluated. The purpose of this study was to evaluate a whole carcass rinse (WCR) and a neck skin excision (NS) procedure for Salmonella and Escherichia coli isolation from the same broiler carcass. Carcasses were obtained from three broiler processing plants. The skin around the neck area was aseptically removed and bagged separately from the carcass, and microbiological analysis was performed. The corresponding carcass was bagged and a WCR sample was evaluated. No significant difference (alpha = 0.05) in Salmonella prevalence was found between the samples processed by the two methods, but both procedures produced many false-negative Salmonella results. Prechill, 37% (66 carcasses), 28% (50 carcasses), and 51% (91 carcasses) of the 180 carcasses examined were positive for Salmonella by WCR, NS, and both procedures combined, respectively. Postchill, 3% (5 carcasses), 7% (12 carcasses), and 10% (17 carcasses) of the 177 carcasses examined were positive for Salmonella by the WCR, NS, and combination of both procedures, respectively. Prechill, E. coli plus coliform counts were 3.0 and 2.6 log CFU/ml by the WCR and NS methods, respectively. Postchill, E. coli plus coliform counts were 1.7 and 1.4 log CFU/ml by the WCR and NS methods, respectively.
Assuntos
Galinhas/microbiologia , Escherichia coli/isolamento & purificação , Manipulação de Alimentos/métodos , Salmonella/isolamento & purificação , Animais , Temperatura Baixa , Contagem de Colônia Microbiana , Indústria de Processamento de Alimentos/métodos , Indústria de Processamento de Alimentos/normas , Humanos , Imersão , Pescoço/microbiologia , Pele/microbiologiaRESUMO
Molecular analysis of five Brazilian families, including eight patients presenting with nonclassic Tay-Sachs disease, was performed to identify frequent causative mutations and their correlation with clinical course. Three patients were affected by the B1 subacute variant and were shown to carry the R178H mutation (the DN allele), which is also common among Portuguese patients. Two of them were compound heterozygotes, whereas the third presented with the mutation in both alleles. Since Brazil was a Portuguese colony for over two centuries, common ancestry might be the probable explanation. The fourth patient presented with a juvenile phenotype and carries the R499H mutation, which has been reported only once worldwide and is associated with residual enzyme activity, responsible for a slower clinical course. The fifth family, of an Ashkenazi Jewish background, showed an extensive intrafamilial clinical variability among three affected sibs presenting with muscle atrophy, ataxia, and psychiatric symptoms. They were first diagnosed as having atypical spinal muscular atrophy and, subsequently, spinocerebellar ataxia, but, recently, the diagnosis of late-onset Tay-Sachs disease was confirmed based on reduced plasma hexosaminidase A activity and the G269S/InsTATC1278 genotype. It is therefore highly recommended to test patients with a similar clinical history for Tay-Sachs disease. In the same family, one first cousin committed suicide at the age of 24 years, presenting with a clinical phenotype that suggested an undiagnosed case and highlighting the effect of the intrafamilial clinical variability in delaying a prompt diagnosis. It is now recognized that his parents are, in fact, a carrier couple. Additionally, another relative had been previously identified as a heterozygote in a Tay-Sachs disease screening program, but the information was not shared among the family. Since this information might anticipate diagnosis and genetic counseling, it is advisable that heterozygote screening programs encourage families to share genetic information.
Assuntos
Mutação/genética , Doença de Tay-Sachs/diagnóstico , Doença de Tay-Sachs/genética , beta-N-Acetil-Hexosaminidases/genética , Adulto , Brasil , Criança , Pré-Escolar , Hexosaminidase A , Humanos , Linhagem , Fenótipo , Doença de Tay-Sachs/complicaçõesRESUMO
Gaucher disease (GD), the most prevalent lysosome storage disorder, presents an autosomal recessive mode of inheritance. It is a paradigm for therapeutic intervention in medical genetics due to the existence of effective enzyme replacement therapy. We report here the analysis of GD in 262 unrelated Brazilian patients, carried out in order to establish the frequency of the most common mutations and to provide prognostic information based on genotype-phenotype correlations. Among 247 type 1 GD patients, mutation N370S was detected in 47% of all the alleles, but N370S/N370S homozygosity was found in only 10% of the patients, a much lower frequency than expected, suggesting that most individuals presenting this genotype may not receive medical attention. Recombinant alleles were detected at a high frequency: 44% of the chromosomes bearing mutation L444P had other mutations derived from the pseudogene sequence, present in 25% of patients. Three neuronopathic type 2 patients were homozygous for L444P, all presenting additional mutations (E326K or recombinant alleles) that probably lead to the more severe phenotypes. Six children, classified as type 1 GD patients, had a L444P/L444P genotype, showing that neuronopathic symptoms may only manifest later in life. This would indicate the need for a higher treatment dose during enzyme replacement therapy. Finally, mutation G377S was present in 4 homozygous type 1 patients and also in compound heterozygosity in 5 (42%) type 3 patients. These findings indicate that G377S cannot be unambiguously classified as mild and suggest an allele-dose effect for this mutation.
Assuntos
Alelos , Doença de Gaucher/genética , Mutação/genética , Análise Mutacional de DNA , Doença de Gaucher/diagnóstico , Testes Genéticos , Genótipo , Humanos , Mucosa Bucal , Fenótipo , Polimorfismo de Fragmento de Restrição , Recombinação GenéticaRESUMO
In mammals, dosage compensation at X-linked loci is achieved by the process of X chromosome inactivation in the homogametic sex. While most genes on the inactive X chromosome (Xi) are subjected to transcriptional inactivation, some escape inactivation and present biallelic expression. The expression status of X-linked genes has been extensively studied in somatic cell hybrids containing only the human Xi. Although this approach has recently been used to generate a profile of X-linked gene activity, it may not reflect what happens in a normal human cell. The recent development of a database of single nucleotide polymorphisms (SNPs) throughout the human genome enables investigation of allele-specific gene expression in normal human cells. In this study, we established a panel of X-linked expressed SNPs (cSNPs). These markers were used for monitoring gene expression in primary human fibroblast cell lines with completely skewed XCI, demonstrating the potential of this system for studying X-linked gene expression in normal human cells.
Assuntos
Alelos , Polimorfismo de Nucleotídeo Único , Cromossomo X/genética , Sequência de Bases , Linhagem Celular , DNA Complementar/genética , Mecanismo Genético de Compensação de Dose , Feminino , Expressão Gênica , Ligação Genética , Marcadores Genéticos , Genótipo , Heterozigoto , Humanos , Hipoxantina Fosforribosiltransferase/genética , MutaçãoRESUMO
X-chromosome inactivation (XCI) is the process by which mammals perform dosage compensation of X-linked gene products between XY males and XX females, resulting in the transcriptional silencing of all but one X chromosome per diploid cell. XCI involves counting the X chromosomes in a cell, randomly choosing those to be inactivated, spreading the inactivation signal in cis throughout the chromosome, and maintaining the inactive state of those X chromosomes during cell divisions thereafter. How the cell performs all these tasks is a fascinating problem and, together with epigenetic inheritance, a basic cellular mechanism that remains to be fully understood. In this review, we describe recent experiments aimed at understanding the first events of XCI and propose a model for initiation of XCI.
Assuntos
Mecanismo Genético de Compensação de Dose , Cromossomo X/genética , Animais , Camundongos , Camundongos Knockout , Camundongos Transgênicos , RNA Longo não Codificante , RNA não Traduzido/genética , Fatores de Transcrição/genéticaRESUMO
Mammals perform dosage compensation of X-linked gene products between XY males and XX females by transcriptionally silencing all but one X chromosome per diploid cell, a process called X chromosome inactivation (XCI). XCI involves counting X chromosomes in a cell, random or imprinted choice of one X to remain active, initiation and spread of the inactivation signal in CIS throughout the other X chromosomes, and maintenance of the inactive state of those X chromosomes during cell divisions thereafter. Most of what is known of the molecular mechanisms involved in the different steps of XCI has been studied in the mouse. In this review we compare XCI in mouse and human, and discuss how much of the murine data can be extrapolated to humans.
Assuntos
Mecanismo Genético de Compensação de Dose , Cromossomo X/genética , Animais , Metilação de DNA , Humanos , Camundongos , RNA Longo não Codificante , RNA não Traduzido/genética , Fatores de Transcrição/genéticaRESUMO
Embryonic stem cells are totipotent cells derived from the inner cell mass of blastocysts. Recently, the development of appropriate culture conditions for the differentiation of these cells into specific cell types has permitted their use as potential therapeutic agents for several diseases. In addition, manipulation of their genome in vitro allows the creation of animal models of human genetic diseases and for the study of gene function in vivo. We report the establishment of new lines of murine embryonic stem cells from preimplantation stage embryos of 129/Sv mice. Most of these cells had a normal karyotype and an XY sex chromosome composition. The pluripotent properties of the cell lines obtained were analyzed on the basis of their alkaline phosphatase activity and their capacity to form complex embryoid bodies with rhythmically contracting cardiomyocytes. Two lines, USP-1 and USP-3, with the best in vitro characteristics of pluripotency were used in chimera-generating experiments. The capacity to contribute to the germ line was demonstrated by the USP-1 cell line. This cell line is currently being used to generate mouse models of human diseases.
Assuntos
Linhagem Celular/citologia , Modelos Animais de Doenças , Embrião de Mamíferos/citologia , Doenças Genéticas Inatas/genética , Células-Tronco/citologia , Fosfatase Alcalina/metabolismo , Animais , Diferenciação Celular , Linhagem Celular/enzimologia , Quimera , Feminino , Doenças Genéticas Inatas/patologia , Células Germinativas , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Células-Tronco/enzimologiaRESUMO
How to measure pain is a great challenge to those who desire to control adequately such a complex experience. Standardized instruments that take into consideration the patient's own account, have been developed in order to make such a task easier. In this article we carry out a revision of the instruments used mostly for measuring postoperative pain, and we point out some of the advantages and disadvantages. We emphasize the need for specific research focusing on the measurement of surgical pain, taking into consideration the multiple dimensions of a painful experience.
Assuntos
Avaliação em Enfermagem/métodos , Medição da Dor/métodos , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/enfermagem , Humanos , Reprodutibilidade dos TestesRESUMO
In this study we investigate the language used by nurses in the characterization of postoperative pain. In order to do this, an instrument was elaborated containing initially 308 pain descriptors, which were studied as to their apparent and content validity. After this study, using 119 descriptors, the instrument was applied to 116 nurses. The category estimation method was used, with scores varying from 1 to 7. The mean score and standard deviation were calculated for the scores obtained. The descriptors of highest ascriptions were, in a decreasing order: intense, strong, acute, unbearable and continuous; those of lower ascriptions were: circulating, assailing, circular, slow and formidable.
Assuntos
Avaliação em Enfermagem/métodos , Medição da Dor/métodos , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/enfermagem , Humanos , Pesquisa em Avaliação de Enfermagem , Semântica , Índice de Gravidade de DoençaRESUMO
DNA methylation is essential in X chromosome inactivation and genomic imprinting, maintaining repression of XIST in the active X chromosome and monoallelic repression of imprinted genes. Disruption of the DNA methyltransferase genes DNMT1 and DNMT3B in the HCT116 cell line (DKO cells) leads to global DNA hypomethylation and biallelic expression of the imprinted gene IGF2 but does not lead to reactivation of XIST expression, suggesting that XIST repression is due to a more stable epigenetic mark than imprinting. To test this hypothesis, we induced acute hypomethylation in HCT116 cells by 5-aza-2'-deoxycytidine (5-aza-CdR) treatment (HCT116-5-aza-CdR) and compared that to DKO cells, evaluating DNA methylation by microarray and monitoring the expression of XIST and imprinted genes IGF2, H19, and PEG10. Whereas imprinted genes showed biallelic expression in HCT116-5-aza-CdR and DKO cells, the XIST locus was hypomethylated and weakly expressed only under acute hypomethylation conditions, indicating the importance of XIST repression in the active X to cell survival. Given that DNMT3A is the only active DNMT in DKO cells, it may be responsible for ensuring the repression of XIST in those cells. Taken together, our data suggest that XIST repression is more tightly controlled than genomic imprinting and, at least in part, is due to DNMT3A.
Assuntos
Metilação de DNA/genética , Repressão Epigenética/genética , Genoma Humano , Genoma/genética , Impressão Genômica/genética , Fator de Crescimento Insulin-Like II/genética , RNA Longo não Codificante/genética , Proteínas Reguladoras de Apoptose , Azacitidina/administração & dosagem , Azacitidina/análogos & derivados , DNA (Citosina-5-)-Metiltransferase 1 , DNA (Citosina-5-)-Metiltransferases/genética , Metilação de DNA/efeitos dos fármacos , Proteínas de Ligação a DNA , Decitabina , Técnicas de Inativação de Genes , Genoma Humano/efeitos dos fármacos , Células HCT116 , Humanos , Hibridização in Situ Fluorescente/métodos , Análise em Microsséries , Polimorfismo de Nucleotídeo Único , Proteínas/metabolismo , RNA Longo não Codificante/metabolismo , Proteínas de Ligação a RNA , Reação em Cadeia da Polimerase em Tempo Real/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , DNA Metiltransferase 3BRESUMO
Marfan syndrome (MFS) is an autosomal dominant disease of the connective tissue that affects the ocular, skeletal and cardiovascular systems, with a wide clinical variability. Although mutations in the FBN1 gene have been recognized as the cause of the disease, more recently other loci have been associated with MFS, indicating the genetic heterogeneity of this disease. We addressed the issue of genetic heterogeneity in MFS by performing linkage analysis of the FBN1 and TGFBR2 genes in 34 families (345 subjects) who met the clinical diagnostic criteria for the disease according to Ghent. Using a total of six microsatellite markers, we found that linkage with the FBN1 gene was observed or not excluded in 70.6% (24/34) of the families, and in 1 family the MFS phenotype segregated with the TGFBR2 gene. Moreover, in 4 families linkage with the FBN1 and TGFBR2 genes was excluded, and no mutations were identified in the coding region of TGFBR1, indicating the existence of other genes involved in MFS. Our results suggest that the genetic heterogeneity of MFS may be greater that previously reported.
Assuntos
Heterogeneidade Genética , Ligação Genética/genética , Síndrome de Marfan/genética , Proteínas dos Microfilamentos/genética , Fator de Crescimento Transformador beta/genética , Distribuição de Qui-Quadrado , Estudos de Coortes , Feminino , Fibrilina-1 , Fibrilinas , Marcadores Genéticos , Humanos , Escore Lod , Masculino , Síndrome de Marfan/diagnóstico , Taxa de MutaçãoAssuntos
Mecanismo Genético de Compensação de Dose , Regiões Promotoras Genéticas , RNA não Traduzido , Fatores de Transcrição/genética , Substituição de Aminoácidos , Análise Mutacional de DNA , Feminino , Testes Genéticos , Humanos , Distrofia Muscular de Duchenne/genética , Mutação , RNA Longo não CodificanteRESUMO
DNA methylation is essential in X chromosome inactivation and genomic imprinting, maintaining repression of XIST in the active X chromosome and monoallelic repression of imprinted genes. Disruption of the DNA methyltransferase genes DNMT1 and DNMT3B in the HCT116 cell line (DKO cells) leads to global DNA hypomethylation and biallelic expression of the imprinted gene IGF2 but does not lead to reactivation of XIST expression, suggesting that XIST repression is due to a more stable epigenetic mark than imprinting. To test this hypothesis, we induced acute hypomethylation in HCT116 cells by 5-aza-2′-deoxycytidine (5-aza-CdR) treatment (HCT116-5-aza-CdR) and compared that to DKO cells, evaluating DNA methylation by microarray and monitoring the expression of XIST and imprinted genes IGF2, H19, and PEG10. Whereas imprinted genes showed biallelic expression in HCT116-5-aza-CdR and DKO cells, the XIST locus was hypomethylated and weakly expressed only under acute hypomethylation conditions, indicating the importance of XIST repression in the active X to cell survival. Given that DNMT3A is the only active DNMT in DKO cells, it may be responsible for ensuring the repression of XIST in those cells. Taken together, our data suggest that XIST repression is more tightly controlled than genomic imprinting and, at least in part, is due to DNMT3A.
Assuntos
Humanos , Metilação de DNA/genética , Repressão Epigenética/genética , Genoma Humano , Genoma/genética , Impressão Genômica/genética , Fator de Crescimento Insulin-Like II/genética , RNA Longo não Codificante/genética , Azacitidina/administração & dosagem , Azacitidina/análogos & derivados , /genética , Metilação de DNA/efeitos dos fármacos , Técnicas de Inativação de Genes , Genoma Humano/efeitos dos fármacos , Hibridização in Situ Fluorescente/métodos , Análise em Microsséries , Polimorfismo de Nucleotídeo Único , Proteínas/metabolismo , RNA Longo não Codificante/metabolismo , Reação em Cadeia da Polimerase em Tempo Real/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodosRESUMO
Gaucher disease is the most frequent lysosome storage disease and presents an autosomal recessive mode of inheritance. It is caused by mutations at the GBA gene leading to deficient activity of the glucocerebrosidase enzyme. This report describes 12 new mutations [c.38A>G (K-27R), c.220G>A (G35S), c.448G>A (E111K), IVS4+1G>A, c.746C>T (A210V), c.776A>G (Y220C), c.793delC (Q226_fs4X), c.1102C>T (R329C), c.1300C>T (R395C), c.1309G>A (V398I), c.1324-1326delATT (delI403) and c.1583T>C (I489T)] and 4 novel silent alterations [c.342C>T (F75), c.528C>T (D137), c.1011C>T (D298) and c.1092G>A (G325)] detected among 40 unrelated Brazilian type 1 Gaucher disease patients by a combination of RFLP, dHPLC and DNA sequencing procedures. The R329C mutation, previously described in a Parkinson's disease patient (A. Lwin, E. Orvisky, O. Goker-Alpan, M.E. LaMarca, E. Sidransky. Glucocerebrosidase mutations in subjects with Parkinsonism. Mol. Genet. Metab. 81 (2004) 70-73), is described here for the first time in a Gaucher disease patient. Several genotype-phenotype correlations could be established, contributing significantly to the panel of reported mutations and conferring predictive value to their detection.
Assuntos
Doença de Gaucher/genética , Glucosilceramidase/genética , Mutação de Sentido Incorreto , Polimorfismo de Fragmento de Restrição , Brasil , Análise Mutacional de DNA , Feminino , Genótipo , Humanos , Masculino , Transtornos Parkinsonianos/genética , Reação em Cadeia da PolimeraseRESUMO
Marfan syndrome (MFS) is an autosomal dominant disease of the connective tissue that affects the ocular, skeletal and cardiovascular systems, with a wide clinical variability. Although mutations in the FBN1 gene have been recognized as the cause of the disease, more recently other loci have been associated with MFS, indicating the genetic heterogeneity of this disease. We addressed the issue of genetic heterogeneity in MFS by performing linkage analysis of the FBN1 and TGFBR2 genes in 34 families (345 subjects) who met the clinical diagnostic criteria for the disease according to Ghent. Using a total of six microsatellite markers, we found that linkage with the FBN1 gene was observed or not excluded in 70.6 percent (24/34) of the families, and in 1 family the MFS phenotype segregated with the TGFBR2 gene. Moreover, in 4 families linkage with the FBN1 and TGFBR2 genes was excluded, and no mutations were identified in the coding region of TGFBR1, indicating the existence of other genes involved in MFS. Our results suggest that the genetic heterogeneity of MFS may be greater that previously reported.