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2.
Arch Dis Child ; 2020 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-32819910

RESUMO

OBJECTIVE: Use next-generation sequencing (NGS) technology to improve our diagnostic yield in patients with suspected genetic disorders in the Asian setting. DESIGN: A diagnostic study conducted between 2014 and 2019 (and ongoing) under the Singapore Undiagnosed Disease Program. Date of last analysis was 1 July 2019. SETTING: Inpatient and outpatient genetics service at two large academic centres in Singapore. PATIENTS: Inclusion criteria: patients suspected of genetic disorders, based on abnormal antenatal ultrasound, multiple congenital anomalies and developmental delay. EXCLUSION CRITERIA: patients with known genetic disorders, either after clinical assessment or investigations (such as karyotype or chromosomal microarray). INTERVENTIONS: Use of NGS technology-whole exome sequencing (WES) or whole genome sequencing (WGS). MAIN OUTCOME MEASURES: (1) Diagnostic yield by sequencing type, (2) diagnostic yield by phenotypical categories, (3) reduction in time to diagnosis and (4) change in clinical outcomes and management. RESULTS: We demonstrate a 37.8% diagnostic yield for WES (n=172) and a 33.3% yield for WGS (n=24). The yield was higher when sequencing was conducted on trios (40.2%), as well as for certain phenotypes (neuromuscular, 54%, and skeletal dysplasia, 50%). In addition to aiding genetic counselling in 100% of the families, a positive result led to a change in treatment in 27% of patients. CONCLUSION: Genomic sequencing is an effective method for diagnosing rare disease or previous 'undiagnosed' disease. The clinical utility of WES/WGS is seen in the shortened time to diagnosis and the discovery of novel variants. Additionally, reaching a diagnosis significantly impacts families and leads to alteration in management of these patients.

3.
Indian J Pediatr ; 2020 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-32648099

RESUMO

Sulphite oxidase deficiency is an extremely rare inborn error of metabolism of sulphur containing amino acids. There are no reports of liver involvement in this condition. The authors describe a 9-y-old boy with known sulphite oxidase deficiency who presented with worsening cholestatic hepatitis which may be possibly related to underlying metabolic disorder. Although there is no current evidence that treating liver disease and ensuring normal hepatic function in sulphite oxidase deficiency would likely benefit patients, this could potentially contribute to optimising growth and development as well as improving the overall prognosis.

4.
J Inherit Metab Dis ; 43(5): 1131-1142, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32233035

RESUMO

Sphingosine-1-phosphate (S1P) lyase is a vitamin B6-dependent enzyme that degrades sphingosine-1-phosphate in the final step of sphingolipid metabolism. In 2017, a new inherited disorder was described caused by mutations in SGPL1, which encodes sphingosine phosphate lyase (SPL). This condition is referred to as SPL insufficiency syndrome (SPLIS) or alternatively as nephrotic syndrome type 14 (NPHS14). Patients with SPLIS exhibit lymphopenia, nephrosis, adrenal insufficiency, and/or neurological defects. No targeted therapy for SPLIS has been reported. Vitamin B6 supplementation has therapeutic activity in some genetic diseases involving B6-dependent enzymes, a finding ascribed largely to the vitamin's chaperone function. We investigated whether B6 supplementation might have activity in SPLIS patients. We retrospectively monitored responses of disease biomarkers in patients supplemented with B6 and measured SPL activity and sphingolipids in B6-treated patient-derived fibroblasts. In two patients, disease biomarkers responded to B6 supplementation. S1P abundance and activity levels increased and sphingolipids decreased in response to B6. One responsive patient is homozygous for an SPL R222Q variant present in almost 30% of SPLIS patients. Molecular modeling suggests the variant distorts the dimer interface which could be overcome by cofactor supplementation. We demonstrate the first potential targeted therapy for SPLIS and suggest that 30% of SPLIS patients might respond to cofactor supplementation.

5.
J Mol Med (Berl) ; 97(11): 1557-1566, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31529142

RESUMO

The VARS2 gene encodes a mitochondrial valyl-transfer RNA synthetase which is used in mitochondrial translation. To date, several patients with VARS2 pathogenic variants have been described in the literature. These patients have features of lactic acidosis with encephalomyopathy. We present a case of an infant with lactic acidosis, failure to thrive, and severe primary pulmonary hypertension who was found to be a compound heterozygote for two novel VARS2 variants (c.1940C>T, p.(Thr647Met) and c.2318G>A, p.(Arg773Gln)). The patient was treated with vitamin supplements and a carbohydrate-restricted diet. The lactic acidosis and failure to thrive resolved, and he showed good growth and development. Functional studies and molecular analysis employed a yeast model system and the VAS1 gene (yeast homolog of VARS2). VAS1 genes harboring either one of two mutations corresponding to the two novel variants in the VARS2 gene, exhibited partially reduced function in haploid yeast strains. A combination of both VAS1 variant alleles in a diploid yeast cell exhibited a more significant decrease in oxidative metabolism-dependent growth and in the oxygen consumption rate (reminiscent of the patient who carries two mutant VARS2 alleles). Our results demonstrate the pathogenicity of the biallellic novel VARS2 variants. KEY MESSAGES: • A case of an infant who is a compound heterozygote for two novel VARS2 variants. • This infant displayed lactic acidosis, failure to thrive, and pulmonary hypertension. • Treatment of the patient with a carbohydrate-restricted diet resulted in good growth and development. • Studies with the homologous yeast VAS1 gene showed reduced function of corresponding single mutant in haploid yeast strains. • A combination of both VAS1 variant alleles in diploid yeast exhibited a more significant decrease in function, thereby confirming the pathogenicity of the biallellic novel VARS2 variants.


Assuntos
Insuficiência de Crescimento/genética , Insuficiência de Crescimento/metabolismo , Antígenos HLA/genética , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/metabolismo , Doenças Mitocondriais/genética , Doenças Mitocondriais/metabolismo , Valina-tRNA Ligase/genética , Alelos , Sequência de Aminoácidos , Heterozigoto , Humanos , Lactente , Masculino , Mutação/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Análise de Sequência de DNA
6.
J Med Case Rep ; 12(1): 208, 2018 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-30007405

RESUMO

BACKGROUND: Urea cycle disorders are secondary to defects in the system converting ammonia into urea, causing accumulation of ammonia and other byproducts which are neurotoxic. Ornithine transcarbamylase deficiency is the most common of the urea cycle disorders and frequently presents with coma or seizures during hyperammonemia. However, seizures can also occur without metabolic decompensation. CASE PRESENTATION: We describe a 23-year-old Chinese woman with urea cycle disorder who presented with confusion due to focal seizures arising from the left frontotemporal region. Interestingly, her ammonia levels remained normal during the seizures. Neuroimaging showed bilateral mesial temporal sclerosis. Her seizures were successfully controlled with two anti-epileptic medications. CONCLUSIONS: This case adds evidence of the predisposition of the temporal lobe to injury in urea cycle disorder. Urea cycle disorder can lead to mesial temporal sclerosis which leads to increased susceptibility of patients to seizures regardless of their metabolic state.


Assuntos
Epilepsias Parciais/diagnóstico , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/patologia , Distúrbios Congênitos do Ciclo da Ureia/diagnóstico , Eletroencefalografia , Epilepsias Parciais/etiologia , Feminino , Humanos , Imagem por Ressonância Magnética , Esclerose/complicações , Esclerose/diagnóstico por imagem , Distúrbios Congênitos do Ciclo da Ureia/complicações , Adulto Jovem
7.
Clin Chim Acta ; 426: 13-7, 2013 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-23994568

RESUMO

BACKGROUND: In the investigation of a proband with a biochemical diagnosis of isolated sulfite oxidase deficiency, we identified a homozygous nonsense mutation of the SUOX gene in the proband. However, the mutation was only detected in the father and not the mother. Deletion of the SUOX gene of the mother and paternal disomy of chromosome 12, where the SUOX gene is located, were suspected in view that allele dropout of the mother non-amplified wild-type allele is unlikely. METHODS: To distinguish the two possible causes, we performed a genome wide microarray analysis in the patient and parents using high-density single-nucleotide microarrays. Whole genome allele sharing of the genomes of the patient and parents were performed by dChip. RESULTS: In the proband, the whole genome scan showed loss of heterozygosity (LOH) of the entire chromosome 12. However, the LOH is copy neutral and deletion of the SUOX gene of the mother was thus excluded. On whole genome allele sharing analysis, the proband showed a high degree of allele sharing with the father and a very low allele sharing with the mother only in chromosome 12. The cause of the homozygosity of the mutation of the patient is UPD (12) pat. CONCLUSIONS: To the best of our knowledge, this study is the first UPD (12) pat causing isolated sulfite oxidase deficiency in humans. Even with one parent being a carrier of an autosomal recessive disease, a fetus with the autosomal recessive disease is still possible. This will have clinical impact on genetic counseling.


Assuntos
Cromossomos Humanos Par 12/genética , Análise de Sequência com Séries de Oligonucleotídeos , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/deficiência , Dissomia Uniparental/genética , Feminino , Humanos , Lactente , Perda de Heterozigosidade/genética , Mutação , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/genética
8.
J Immunol ; 187(1): 462-71, 2011 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-21613618

RESUMO

CD4(+) memory/effector T cells play a central role in orchestrating the rapid and robust immune responses upon re-encounter with specific Ags. However, the immunologic mechanism(s) underlying these responses are still not fully understood. To investigate this, we generated an allergen (major house dust mite allergen, Blo t 5)-specific murine Th2 cell line that secreted IL-4, IL-5, IL-10, and IL-13, but not IL-9 or TNF-α, upon activation by the cognate Ag. These cells also exhibited CD44(high)CD62L(-) and CD127(+) (IL-7Rα(+)) phenotypes, which are characteristics of memory/effector T cells. Experiments involving adoptive transfer of this Th2 cell line in mice, followed by three intranasal challenges with Blo t 5, induced a dexamethasone-sensitive eosinophilic airway inflammation. This was accompanied by elevation of Th2 cytokines and CC- and CXC-motif chemokines, as well as recruitment of lymphocytes and polymorphic mononuclear cells into the lungs. Moreover, Blo t 5-specific IgE was detected 4 d after the last intranasal challenge, whereas elevation of Blo t 5-specific IgG1 was found at week two. Finally, pulmonary delivery of the pVAX-IL-35 DNA construct effectively downregulated Blo t 5-specific allergic airway inflammation, and i.m. injection of pVAX-IL-35 led to long-lasting suppression of circulating Blo t 5-specific and total IgE. This model provides a robust research tool to elucidate the immunopathogenic role of memory/effector Th2 cells in allergic airway inflammation. Our results suggested that IL-35 could be a potential therapeutic target for allergic asthma through its attenuating effects on allergen-specific CD4(+) memory/effector Th2 cell-mediated airway inflammation.


Assuntos
Antígenos de Plantas/imunologia , Imunoglobulina E/biossíntese , Memória Imunológica , Mediadores da Inflamação/fisiologia , Subunidade p35 da Interleucina-12/fisiologia , Pulmão/imunologia , Ácaros/imunologia , Células Th2/imunologia , Alérgenos , Animais , Linhagem Celular , Células Cultivadas , Poeira , Epitopos de Linfócito T/imunologia , Feminino , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/patologia , Pulmão/metabolismo , Pulmão/patologia , Camundongos , Camundongos Endogâmicos C57BL , Células Th2/metabolismo , Células Th2/patologia
9.
Curr Opin Lipidol ; 21(2): 123-7, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20125008

RESUMO

PURPOSE OF REVIEW: Genome-wide association studies (GWASs) and the resequencing of extremes are two methods currently being used to identify the causative variants in dyslipidemia. RECENT FINDINGS: GWASs are high-throughput, array-based platforms. They are nonhypothesis-based and scan within and across many genes. Associated variants identified via GWAS are likely to be common, have modest effect sizes, and are more likely to be a disease marker rather than the true causative variant. Currently, GWAS-identified variants explain only a small amount of heritability associated with dyslipidemia. Resequencing of extremes involves deep sequencing of two groups of individuals, one at each extreme of the phenotype. It is usually used to evaluate genomic regions with a high prior index of suspicion (e.g. genes underlying strong linkage peaks). The associations detected are more likely to reflect causative variants of larger effect size than GWAS-identified variants. The proportion of heritability associated with dyslipidemia explained by rare variants is currently unknown. SUMMARY: Both methods have identified variants that are associated with dyslipidemia and will continue to be used as they play complementary roles.


Assuntos
Dislipidemias/genética , Estudo de Associação Genômica Ampla/métodos , Fenótipo , Análise de Sequência de DNA/métodos , Animais , Humanos
10.
Cell Signal ; 20(12): 2247-55, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18804162

RESUMO

Here we report the cloning and characterization of a novel PDE4D isoform (PDE4D11) identified in mouse brain cDNA. This novel isoform has a unique isoform-specific 5'-UTR and N-terminal sequence, whereas, downstream regulatory N-terminal and catalytic C-terminal regions are homologous to other long PDE4D isoforms (Ex2-15). In silico analysis of PDE4D11 cDNA transcript identified the predicted translational start site and the use of a different transcriptional start site compared to other PDE4D isoforms. This isoform is ubiquitously expressed in different mouse tissues, particularly in the brain, liver and spleen. In the brain, PDE4D11 expression levels increased in the cerebellum, but decreased in the hippocampus with progressive age, highlighting a potential role for this isoform in the development of the brain. When transfected in vitro into murine neuroblastoma cells PDE4D11_EGFP expression is cytosolic, consistent with other long PDE4D isoforms. The appearance of cytosolic protein aggregates in discrete microdomains with this isoform, however, may represent a method of compartmentalizing PDE4D11 activity. The novel 5'-sequence of PDE4D11 is conserved among higher vertebrates including human, monkey, dog, horse and rat. Identification of this new isoform highlights the mutliplicity of unique PDE4D isoforms and their potential importance in regulating cAMP levels through compartmentalization and cell-specific expression and underscores the importance of understanding the functional role of each isoform in the development of specific drugs for the treatment of memory disorders.


Assuntos
Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/metabolismo , Regiões 5' não Traduzidas/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , AMP Cíclico/metabolismo , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/genética , Éxons/genética , Humanos , Íntrons/genética , Camundongos , Camundongos Endogâmicos C57BL , Microscopia de Fluorescência , Dados de Sequência Molecular , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa
11.
Immunology ; 125(2): 218-28, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18355243

RESUMO

Lipopolysaccharide (LPS) is a major component of environmental microbial products. Studies have defined the LPS dose as a critical determining factor in driving differential T-cell polarization but the direct effects of LPS on individual antigen-presenting cells is unknown. Here, we investigated the effects of LPS doses on naive B cells and the subsequent modulatory effects of these LPS-activated B cells on T-cell polarization. The LPS was able to induce a proliferative response starting at a dose of 100 ng/ml and was capable of enhancing antigen internalization at a dose of 1 microg/ml in naive B cells. Following LPS stimulation, up-regulation of the surface markers CD40, CD86, I-Ad, immunoglobulin M, CD54 and interleukin-10 production, accompanied by down-regulation of CD5 and CD184 (CXCR4) were observed in a LPS dose-dependent manner. Low doses (<10 ng/ml) of LPS-activated B cells drove T helper type 2 polarization whereas high doses (>0.1 microg/ml) of LPS-activated B cells resulted in T regulatory type 1 cell polarization. In conclusion, LPS-activated B cells acquire differential modulatory effects on T-cell polarization. Such modulatory effects of B cells are dependent on the stimulation with LPS in a dose-dependent manner. These observations may provide one of the mechanistic explanations for the influence of environmental microbes on the development of allergic diseases.


Assuntos
Linfócitos B/imunologia , Lipopolissacarídeos/imunologia , Cooperação Linfocítica/imunologia , Linfócitos T/imunologia , Animais , Antígenos de Superfície/metabolismo , Polaridade Celular/imunologia , Proliferação de Células , Células Cultivadas , Relação Dose-Resposta Imunológica , Endocitose/imunologia , Interleucina-10/biossíntese , Lectinas Tipo C/imunologia , Ativação Linfocitária/imunologia , Lectinas de Ligação a Manose/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Pinocitose , Receptores de Superfície Celular/imunologia , Baço/imunologia , Regulação para Cima/imunologia
12.
Pediatr Allergy Immunol ; 19(5): 399-407, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18221468

RESUMO

Fish allergy is common in countries where consumption is high. Asian nations are amongst the world's largest consumers of fish but the allergen profiles of tropical fish are unknown. This study sought to evaluate the allergenicity of four commonly consumed tropical fish, the threadfin (Polynemus indicus), Indian anchovy (Stolephorus indicus), pomfret (Pampus chinensis) and tengirri (Scomberomorus guttatus). Immunoglobulin E (IgE) cross-reactivity with parvalbumin of cod fish (Gad c 1), the major fish allergen, was also studied. Detection of tropical fish and cod specific-IgE was performed by UniCap assay, and skin prick tests were also carried out. The IgE-binding components of tropical fish were identified using IgE immunoblot techniques, and cross-reactivity with Gad c 1 was assessed by ELISA inhibition and IgE immunoblot inhibition. Clinically, nine of 10 patients studied were allergic to multiple fish. All patients exhibited detectable specific-IgE to cod fish (10 of 10 skin prick test positive, eight of 10 UniCap assay positive) despite lack of previous exposure. The major allergen of the four tropical fish was the 12-kDa parvalbumin. IgE cross-reactivity of these allergens to Gad c 1 was observed to be moderate to high in the tropical fish studied. Parvalbumins are the major allergens in commonly consumed tropical fish. They are cross-reactive with each other as well as with Gad c 1. Commercial tests for cod fish appear to be sufficient for the detection of tropical fish specific-IgE.


Assuntos
Alérgenos/efeitos adversos , Produtos Pesqueiros/efeitos adversos , Proteínas de Peixes/imunologia , Hipersensibilidade Alimentar/imunologia , Gadiformes , Parvalbuminas/imunologia , Adulto , Alérgenos/sangue , Alérgenos/imunologia , Animais , Criança , Reações Cruzadas/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Proteínas de Peixes/efeitos adversos , Proteínas de Peixes/sangue , Hipersensibilidade Alimentar/sangue , Hipersensibilidade Alimentar/fisiopatologia , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Masculino , Parvalbuminas/efeitos adversos , Parvalbuminas/sangue
13.
Cell Signal ; 20(1): 139-53, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18006274

RESUMO

We report here the cloning and characterization of short and supershort mouse PDE4D isoforms. PDE4D is one of the phosphodiesterase enzyme families with multiple promoters and splice variants. PDE4 isoforms present in humans, rats and mice share considerable homology in their catalytic and regulatory domains. In this study, we have identified the novel PDE4D2 variant3 (PDE4D2v3) and PDE4D10 isoforms and the mouse orthologs of PDE4D1, PDE4D2 variant1 (PDE4D2v1), PDE4D2 variant2 (PDE4D2v2) and PDE4D6 isoforms. These isoforms have many different lengths of 5'UTR, signifying the use of different transcription start sites. Our data indicate that many novel PDE4D isoforms exist as a result of alternative mRNA splicing, each isoform having unique N-terminal regions and multiple transcription start sites. Subcellular distribution study showed that the PDE4D1 short isoforms are localized to the nucleus while the supershort isoforms (PDE4D2v1, PDE4D2v2, PDE4D2v3, PDE4D6 and PDE4D10) are restricted to the cytoplasm. Deletion study confirmed that the N-terminus of PDE4D1 is necessary for nuclear targeting. In addition, we showed that the unique N-terminus contains nuclear localization signal sequence. Identifying novel tissue-specific PDE4D isoforms with unique N-terminal regions may aid in the development of selective phosphodiesterase inhibitors.


Assuntos
Núcleo Celular/enzimologia , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/genética , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/metabolismo , Citoplasma/enzimologia , Transdução de Sinais/fisiologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Éxons/genética , Fibroblastos/citologia , Fibroblastos/enzimologia , Íntrons/genética , Isoenzimas/genética , Isoenzimas/metabolismo , Camundongos , Dados de Sequência Molecular , Células NIH 3T3 , Regiões Promotoras Genéticas/genética , Transfecção
14.
BMC Cancer ; 6: 261, 2006 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-17078893

RESUMO

BACKGROUND: From 1968 to 2002, Singapore experienced an almost three-fold increase in breast cancer incidence. This increase appeared to be different across the three main ethnic groups: Chinese, Malays and Indians. This paper used age-period-cohort (APC) modelling, to determine the effects of age at diagnosis, calendar period, and birth cohort on breast cancer incidence for each ethnic group. METHODS: This study included all breast cancer cases (n = 15,269) in the three ethnic groups, reported to the Singapore Cancer Registry from 1968 to 2002 between the ages 25 to 79. Age-specific fertility rates from the Department of Statistics were used to explore the role of fertility. RESULTS: In the 1970s, Indian women had the highest age-standardized breast cancer but by the mid-1980s the highest rates were seen among the Chinese. Remarkable differences were seen in the age-specific incidence rates by ethnic groups. After age 49, the incidence rates for the Chinese and Malays leveled off whereas it continued to rise in the Indians. While our analyses provided some evidence that an age-drift model described the trend seen in the Indians, age-period-cohort model and age-cohort model had the best fit for the Chinese and Malays aged 25 to 79 respectively. Overall, Chinese and Malay women born in later cohorts were at increased risk of developing breast cancer relative to their counterparts in the earlier cohorts. The three ethnic groups experienced similar changes in their fertility in the 1970s, which likely explained much of the increase in their breast cancer incidence but not the ethnic differences. There was a stronger inverse association between total fertility rate and pre-menopausal breast cancer incidence in the Chinese and Malays than the Indians. CONCLUSION: The observed dissimilarity among ethnic groups suggests ethnic differences in exposure or response to certain risk factors. It is likely that longer and subtler differences in childbearing trends and other risk factors may further explain these ethnic differences.


Assuntos
Neoplasias da Mama/etnologia , Neoplasias da Mama/epidemiologia , Adulto , Idade de Início , Idoso , China/etnologia , Estudos de Coortes , Feminino , Fertilidade , Humanos , Incidência , Índia/etnologia , Malásia/etnologia , Pessoa de Meia-Idade , Fatores de Risco , Singapura/epidemiologia
15.
Ann Acad Med Singap ; 35(12): 901-4, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17219004

RESUMO

INTRODUCTION: Williams syndrome (WS) is a rare but well recognised neurodevelopmental disease affecting the connective tissue and the central nervous system. Many patients are identified through the presence of dysmorphic features and associated cardiac abnormalities. Klinefelter syndrome (KS) is associated with gynaecomastia, small testes, azoospermia and elevated gonadotropin levels. They are recognised in the second decade of life by their tall stature and delay in pubertal development. A combination of constitutive WS and KS has yet to be described. CLINICAL PICTURE: We report a child with these genetic aberrations, highlighting the clinical characteristics of such an individual. CONCLUSION: The manifestations and interactions of both conditions are also discussed.


Assuntos
Síndrome de Klinefelter/epidemiologia , Síndrome de Williams/epidemiologia , Estatura , Peso Corporal , Pré-Escolar , Comorbidade , Humanos , Hibridização in Situ Fluorescente , Síndrome de Klinefelter/diagnóstico , Masculino , Síndrome de Williams/diagnóstico
17.
Emerg Infect Dis ; 10(2): 232-4, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15030688

RESUMO

Secondary household transmission of severe acute respiratory syndrome (SARS) was studied in 114 households involving 417 contacts. The attack rate was low (6.2%). Occupation of the index case was the factor that most influenced household transmission (adjusted hazard ratio for healthcare workers 0.157; 95% confidence interval 0.042 to 0.588).


Assuntos
Síndrome Respiratória Aguda Grave/transmissão , Adolescente , Adulto , Idoso , Busca de Comunicante , Características da Família , Feminino , Pessoal de Saúde , Humanos , Transmissão de Doença Infecciosa do Profissional para o Paciente , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Síndrome Respiratória Aguda Grave/epidemiologia , Singapura/epidemiologia , Fatores de Tempo
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