RESUMO
Holt-Oram syndrome (HOS) is an autosomal dominant condition affecting the heart and upper limbs. We have sought to identify the location of this gene using microsatellite DNA markers in a linkage study. Of seven families analysed, five show linkage between HOS and markers on chromosome 12q. But the two remaining families, phenotypically indistinguishable from the others, do not show this linkage. Analysis with the computer program HOMOG indicates that HOS is a heterogeneous disease. Our analysis places one HOS locus in a 21 cM interval in the distal region of chromosome 12q. The localization of a gene for HOS, reported here, represents an important step towards a better understanding of limb and cardiac development.
Assuntos
Anormalidades Múltiplas/genética , Braço/anormalidades , Cromossomos Humanos Par 12 , Genes Dominantes , Deformidades Congênitas da Mão/genética , Cardiopatias Congênitas/genética , Anormalidades Múltiplas/classificação , Mapeamento Cromossômico , Troca Genética , DNA Satélite/genética , Feminino , Marcadores Genéticos , Deformidades Congênitas da Mão/classificação , Cardiopatias Congênitas/classificação , Humanos , Masculino , Linhagem , SíndromeRESUMO
Holt-Oram syndrome is a developmental disorder affecting the heart and upper limb, the gene for which was mapped to chromosome 12 two years ago. We have now identified a gene for this disorder (HOS1). The gene (TBX5) is a member of the Brachyury (T) family corresponding to the mouse Tbx5 gene. We have identified six mutations, three in HOS families and three in sporadic HOS cases. Each of the mutations introduces a premature stop codon in the TBX5 gene product. Tissue in situ hybridization studies on human embryos from days 26 to 52 of gestation reveal expression of TBX5 in heart and limb, consistent with a role in human embryonic development.
Assuntos
Anormalidades Múltiplas/genética , Braço/anormalidades , Cardiopatias Congênitas/genética , Proteínas com Domínio T , Fatores de Transcrição/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Linhagem Celular , Cromossomos Artificiais de Levedura , Cromossomos Humanos Par 12 , DNA , Proteínas de Ligação a DNA/genética , Embrião de Mamíferos/metabolismo , Feminino , Proteínas Fetais/genética , Expressão Gênica , Humanos , Masculino , Camundongos , Dados de Sequência Molecular , Família Multigênica , Linhagem , RNA Mensageiro/genética , Homologia de Sequência de Aminoácidos , Síndrome , Transcrição Gênica , Translocação GenéticaRESUMO
Pericentric inversion of chromosome 9 involving the qh region is relatively common as a constitutional genetic aberration without any apparent phenotypic consequences. However, it has not been established as an acquired abnormality in cancer. Among the three patients reported so far in the literature with acquired inv(9), only one had acute myeloid leukemia (AML). Here we describe an unique case where both chromosomes 9 presented with an acquired pericentric inversion with breakpoints at 9p13 and 9q12 respectively, in a AML patient with aberrant CD7 and CD9 positivity. Additionally, one der(9) also showed short arm deletion at 9p21 to the centromeric region and including the p16 gene. The constitutional karyotype was normal. This is probably the first report describing an acquired inv(9) involving both chromosomes 9 in AML. The possible significance of this inversion is discussed.
Assuntos
Inversão Cromossômica , Cromossomos Humanos Par 9 , Leucemia Mieloide Aguda/genética , Antígenos CD/biossíntese , Antígenos CD7/biossíntese , Bandeamento Cromossômico , Deleção Cromossômica , Mapeamento Cromossômico , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Glicoproteínas de Membrana/biossíntese , Tetraspanina 29RESUMO
We describe a case of acute myeloid leukemia (AML) in which trisomy 21 was the sole acquired cytogenetic abnormality. The immunophenotype showed positivity for CD7 and CD9 along with CD13, CD33, and CD34. The chromosomal analysis of bone marrow showed 47,XY +21 in all the metaphases analyzed. The constitutional karyotype was normal. The patient was an adult and did not have any features of Down's syndrome. The bone marrow morphology was AML-M2 as per the French-American-British (FAB) criteria. A final diagnosis of CD7- and CD9-positive AML-M2 was established with trisomy 21 as a sole cytogenetic abnormality. The patient responded remarkably well to chemotherapy and achieved complete clinical remission. This is the first case of CD7- and CD9-positive AML with trisomy 21 as a sole abnormality. A putative role for the co-expression of abnormal lymphoid markers in achieving quick remission is discussed.
Assuntos
Antígenos CD7 , Antígenos CD , Síndrome de Down/diagnóstico , Síndrome de Down/genética , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Glicoproteínas de Membrana , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medula Óssea/patologia , Citarabina/administração & dosagem , Análise Citogenética , Daunorrubicina/administração & dosagem , Síndrome de Down/complicações , Humanos , Cariotipagem , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Indução de Remissão , Tetraspanina 29 , Resultado do TratamentoRESUMO
Linkage analysis using the polymorphic loci DXS369, DXS296, DXS297 and DXS306 was carried out on a cohort of 17 families segregating for fragile X syndrome. The observed recombination fractions at: DXS369 (Zmax = 3.02; theta = 0.06), DXS297 (Zmax = 2.92; theta = 0.0), DXS296 (Zmax = 3.82; theta = 0.0), DXA306 (Zmax = 4.55; theta = 0.05) confirm that these loci are tightly linked to FRAXA. Our experience in the cytogenetic analysis of 58 at risk pregnancies by chorionic villus or fetal blood sample examination documents a false negative rate in obligate carrier male pregnancies for CVS of 11% and for FBS of 3%.
Assuntos
Síndrome do Cromossomo X Frágil/genética , Citogenética , DNA/genética , Feminino , Síndrome do Cromossomo X Frágil/diagnóstico , Triagem de Portadores Genéticos , Ligação Genética , Marcadores Genéticos , Humanos , Masculino , Polimorfismo Genético , Gravidez , Diagnóstico Pré-NatalRESUMO
A new technique is described for studying antibiotic concentrations in an experimental inflammatory exudate in vivo. In most exudates concentrations of four antistaphylococcal drugs which were of potential therapeutic significance could be assayed, and fucidin appeared to diffuse best. Higher concentrations of all antibiotics gained access to the lesion in the first two hours of inflammation, suggesting that their mobility did not depend on binding to cells during the inflammatory response. The technique may ultimately help to elucidate the relationship between antibiotics and host defences at the primary sites of infection.
Assuntos
Antibacterianos/metabolismo , Exsudatos e Transudatos/metabolismo , Inflamação/metabolismo , Adulto , Cefalosporinas/metabolismo , Cloxacilina/metabolismo , Ácido Fusídico/sangue , Ácido Fusídico/metabolismo , Glicosídeos/metabolismo , Humanos , Inflamação/tratamento farmacológico , Métodos , Pirrolidinas/metabolismo , Técnica de Janela Cutânea , Fatores de TempoRESUMO
Human phagocytic cells are of crucial importance in the early responses to infection. However, tests of their function have been somewhat neglected in immunological screening. This paper summarises briefly our techniques for studying neutrophils and monocytes in skin abrasions and a simple assay of phagocytic and bactericidal function. These techniques use small volumes of blood and are suitable for inclusion in the early screening of individuals who have repeated bacterial infections.
Assuntos
Inflamação/fisiopatologia , Fagocitose , Humanos , Fagócitos/fisiologiaAssuntos
Diatrizoato/metabolismo , Iodo/sangue , Testes de Função Tireóidea , Urografia , Adulto , Idoso , Proteínas Sanguíneas , Creatinina/metabolismo , Feminino , Humanos , Hipertireoidismo/sangue , Infusões Parenterais , Injeções Intravenosas , Iodoproteínas/sangue , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Fatores de Tempo , UreterAssuntos
Diagnóstico Pré-Natal/métodos , Fibrose Cística/diagnóstico , Regulador de Condutância Transmembrana em Fibrose Cística , Desenvolvimento Embrionário , Ética Médica , Feminino , Doenças Genéticas Inatas , Heterozigoto , Humanos , Proteínas de Membrana/genética , Reação em Cadeia da Polimerase , Gravidez , Deleção de SequênciaAssuntos
Infecções/imunologia , Leucócitos/imunologia , Formação de Anticorpos , Reações Antígeno-Anticorpo , Infecções Bacterianas/imunologia , Quimiotaxia , Histocitoquímica , Humanos , Imunidade Celular , Imunoglobulinas/fisiologia , Síndromes de Imunodeficiência/imunologia , Técnicas Imunológicas , Recém-Nascido , Inflamação , Linfócitos/imunologia , Testes de Sensibilidade Microbiana , Fagocitose , Viroses/imunologiaAssuntos
Fibrose Cística/complicações , Infecções Respiratórias/etiologia , Adolescente , Criança , Pré-Escolar , Feminino , Infecções por Haemophilus/etiologia , Infecções por Haemophilus/imunologia , Haemophilus influenzae/imunologia , Humanos , Imunodifusão , Imunoglobulina A/análise , Imunoglobulina G/análise , Imunoglobulina M/análise , Lactente , Masculino , Infecções por Pseudomonas/etiologia , Infecções por Pseudomonas/imunologia , Pseudomonas aeruginosa/imunologia , Infecções Respiratórias/imunologia , Infecções Estreptocócicas/etiologia , Infecções Estreptocócicas/imunologia , Streptococcus/imunologiaRESUMO
This paper describes the genetic services in the United Kingdom and how the evolution of genetic screening services is taking place. Since these Community Genetic Services depend on the offer of a screening test that affects the whole population, it is essential that the community is given genetic education and an opportunity to discuss the issues before services are initiated. In this way, the differing beliefs and needs of individual communities are appropriately taken into account. The development of screening services for cystic fibrosis will show whether this community-orientated model can be successful.
Assuntos
Atenção à Saúde/organização & administração , Testes Genéticos/organização & administração , Serviços de Saúde Comunitária/organização & administração , Triagem de Portadores Genéticos , Implementação de Plano de Saúde , Humanos , Equipe de Assistência ao Paciente/organização & administração , Serviços de Saúde Escolar/organização & administração , Reino Unido , Recursos HumanosRESUMO
Measurement of tissue antibiotic levels is of great importance in developing rational treatment for infection, particularly in patients whose host defense systems are compromised. This review outlines some of the main approaches to this problem, giving examples of the application of the new techniques in different clinical situations.
Assuntos
Antibacterianos/metabolismo , Infecções Bacterianas/tratamento farmacológico , Modelos Biológicos , Antibacterianos/uso terapêutico , Infecções Bacterianas/metabolismo , Vesícula/metabolismo , Espaço Extracelular/análise , Exsudatos e Transudatos/análise , Humanos , Métodos , Testes de Sensibilidade Microbiana , Técnica de Janela Cutânea , Manejo de Espécimes , Escarro/análise , Distribuição TecidualRESUMO
We investigated the knowledge of cystic fibrosis and the views about neonatal and carrier screening in 216 school students aged 14 to 16 years. This work was completed before the published identification of the cystic fibrosis gene in September 1989. Although initial knowledge of cystic fibrosis was low (only 17% of the students knew that the disease affected the lungs), there was good recall of basic information about cystic fibrosis and of recessive inheritance after a brief lecture. A total of 86% considered that carrier detection should be offered routinely and 88% felt that an offer of prenatal diagnosis for cystic fibrosis should be made if both prospective parents were known to be carriers. We believe that pilot studies of cystic fibrosis carrier screening in schools should be undertaken.
Assuntos
Fibrose Cística/prevenção & controle , Triagem de Portadores Genéticos , Educação em Saúde , Programas de Rastreamento/psicologia , Diagnóstico Pré-Natal/psicologia , Psicologia do Adolescente , Adolescente , Atitude Frente a Saúde , Fibrose Cística/psicologia , Feminino , Humanos , Masculino , Opinião Pública , EscóciaRESUMO
OBJECTIVES: To assess the feasibility of detecting consanguineous relationships and significant genetic morbidity through screening pedigrees administered by a primary care trained linkworker. SUBJECTS AND METHODS: A case-controlled crossover study with pedigree recording by both genetic nurse specialists and a primary care worker. From 1012 records of British Pakistani patients registered with an inner city practice, 14 women, identified as having increased genetic risk, were recruited (Group 1). A further 14 age- and parity-matched women, with no indication of genetic morbidity in their General Practice records (Group 2), were also recruited. RESULTS: Valuable genetic information, not recorded in General Practice records, were ascertained through the screening pedigrees, in four members of Group 1 (29%) and six members of Group 2 (43%). There was poor agreement between the coefficients of inbreeding recorded from pedigrees prepared by the primary care worker and genetic nurse specialists (Kappa = 0.157; 95% CI 0.028-0.286). CONCLUSION: Pedigrees can be utilized as a General Practice screening tool to detect relevant genetic morbidity, not ascertained in General Practice records. The process is enhanced when a primary care worker, from the same culture as the volunteers, collects information using the patients' mother tongue.
Assuntos
Consanguinidade , Doenças Genéticas Inatas/prevenção & controle , Testes Genéticos/métodos , Linhagem , Atenção Primária à Saúde/métodos , Adulto , Estudos de Casos e Controles , Estudos Cross-Over , Estudos de Viabilidade , Feminino , Humanos , Entrevistas como Assunto , Idioma , Pessoa de Meia-Idade , Paquistão/etnologia , Projetos Piloto , Especialidades de Enfermagem , Reino UnidoRESUMO
A severely mentally subnormal child with many physical stigmata was shown to have the karyotype 46,XY,-2,+der(2),t(2;10)(q31;q24)pat. Full evaluation of this patient's karyotype depended on the family studies. It was shown that a balanced translocation t(2,10) was present in 4 normal males in 3 generations.