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1.
Community Dent Health ; 30(4): 200-3, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24575522

RESUMO

This paper describes the principles applied and the challenges met while seeking user and other stakeholder perspectives before designing an oral care training package for carers in nursing and residential care facilities. The public health competencies it illustrates include the application of appropriate leadership styles, strategic management, collaborative working and knowledge of research methodology.


Assuntos
Cuidadores/educação , Educação em Saúde Bucal , Capacitação em Serviço/métodos , Recursos Humanos de Enfermagem/educação , Assistência Odontológica para Idosos , Inglaterra , Instituição de Longa Permanência para Idosos , Humanos , Capacitação em Serviço/organização & administração , Casas de Saúde , Técnicas de Planejamento
2.
Community Dent Health ; 29(3): 195-7, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23038933

RESUMO

Practitioners in Dental Public Health often need to find more cost-efficient ways of providing services, whilst assisting with the personal and professional development of colleagues. This paper gives an example of how these competencies were deployed in relation to an epidemiology programme.


Assuntos
Odontologia , Pessoal de Saúde , Doenças Estomatognáticas/epidemiologia , Estudos Epidemiológicos , Avaliação de Resultados em Cuidados de Saúde , Reino Unido/epidemiologia , Recursos Humanos
3.
Artigo em Alemão | MEDLINE | ID: mdl-21887616

RESUMO

OBJECTIVE: To review four key topics pertaining to the oral health of the United Kingdom (UK): (1) provision of state-funded dentistry, (2) trends in oral health, (3) dental caries prevention, and (4) determinants of dental health. METHODS: Data were abstracted, mainly from peer-reviewed publications in the literature. Information was updated where appropriate. RESULTS: Since the 1948 inception of the National Health Service (NHS) and its General Dental Service (GDS), the system of providing dentistry has evolved in response to changing fiscal and health circumstances. Since the 1970s, the oral health of the population, both children's dental decay experience and the decline adult tooth loss, has improved steadily and substantially. Approaches towards prevention are discussed and the dominant position of water fluoridation highlighted. The determinants of dental health are analysed. CONCLUSION: Dental caries experience of children in the UK and the rest of Europe is highly correlated with national wealth as are two other significant determinants: fluoride toothpaste and sugar consumption. The activity of dental professionals appears to have only a limited influence on levels of oral health. There is reason to believe that UK water fluoridation coverage may broaden.


Assuntos
Assistência Odontológica/tendências , Cárie Dentária/prevenção & controle , Medicina Estatal/tendências , Adulto , Criança , Comparação Transcultural , Estudos Transversais , Índice CPO , Cárie Dentária/epidemiologia , Fluoretação/tendências , Humanos , Saúde Bucal/tendências , Fatores Socioeconômicos , Reino Unido
4.
Community Dent Health ; 28(1): 34-9, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21485232

RESUMO

OBJECTIVE: To estimate the potential reduction in dental caries among 5-6-year-old children in a city in the South West of England after six years of water fluoridation. METHOD: Thirteen out of 35 inner city wards and seven out of 43 outer city wards (sharing the same water supply) having the highest mean dmft of 5-6-year-olds (recorded in a census survey in 2005/6) and/or highest indexes of multiple deprivation (IMD) were the principal focal point. Population demographic data and 5-6-year-old caries prevalence and experience were examined. Mean IMD scores and aggregated, weighted mean values for dmft and caries prevalence were referred to previously published regression analyses of caries levels plotted against IMD for 34 fluoridated (F) and 233 non-fluoridated (NF) health districts in England in order to estimate potential caries reductions. RESULTS: Mean dmft of 5-6-year-olds in the 20 wards with the highest caries levels and/or social deprivation was 2.10 (95% CI 1.87, 2.33) and caries prevalence 49% (95% CI 47%, 52%). In three wards, mean dmft exceeded 2.60. Population of the selected wards was approximately 210,800 with a mean IMD score of 33.70 As a conservative estimate, after six years of fluoridation a caries reduction of > 40% could be expected in 5-6-year-olds for the conurbation overall and for the 20 high caries/high IMD wards, with a gain of 12 percentage points in the absolute proportion caries-free. The overall population of the 78 wards served by the three relevant water treatment works identified was approximately 700,000. CONCLUSIONS: On the basis of current caries levels and population demographics, it appears that a comprehensive fluoridation scheme covering the inner and outer city districts would substantially improve the dental health of the city's children.


Assuntos
Cárie Dentária/prevenção & controle , Fluoretação , Planejamento em Saúde/métodos , Criança , Pré-Escolar , Intervalos de Confiança , Índice CPO , Cárie Dentária/epidemiologia , Inglaterra/epidemiologia , Previsões , Humanos , Funções Verossimilhança , Prevalência , Carência Psicossocial , Análise de Regressão , Medição de Risco , População Urbana
5.
Community Dent Health ; 25(2): 70-8, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18637317

RESUMO

OBJECTIVE: To investigate, from current cross-sectional data, the relationships between dental caries experience of 12-year-old children in 29 countries of Europe and four independent variables: national wealth (GDP), expressed as purchasing power parity (PPP x 1,000US$)/ capita/year; population per active dentist; sugar consumption, expressed as Kg/capita/year; and volume sales of toothpaste, expressed as litres/capita/year. METHOD: Most of the data were abstracted from relevant websites. Information on toothpaste sales was from personal communication and obtainable for 16 countries of Western Europe only. Relationships were examined using Spearman's rank correlation method. RESULTS: Mean DMFT showed a strong negative association with national GDP (rho = -0.729, p < 0.01), whilst toothpaste sales showed a statistically significant positive association with GDP (rho = 0.599, p < 0.05) as did sugar consumption (rho = 0.575, p < 0.01). Paradoxically, caries experience yielded a strong negative correlation with sugar consumption (rho = -0.561, p < 0.01) such that ranked increases in mean DMFT were significantly associated with decreasing levels of sugar consumption. None of the other rank correlations was statistically significant. CONCLUSIONS: Unavoidable shortcomings of the available data and their incompleteness meant that any conclusions that could be drawn were speculative. A possible explanation for the anomalous association of low mean DMFT with high sugar consumption in Western Europe is that the extensive use of, mainly fluoride containing, toothpaste neutralises the potential damage from high sugar consumption. Use of sugar principally as a commercial food or drink additive in modern times, with potential for buffering of its acidic fermentation products, together with a possibly more rapid oral clearance of sugar in additive form, may also be a contributory factor.


Assuntos
Cárie Dentária/epidemiologia , Criança , Estudos Transversais , Índice CPO , Odontólogos/provisão & distribuição , Sacarose Alimentar/economia , Economia , Europa (Continente)/epidemiologia , Humanos , Modelos Lineares , Prevalência , Cremes Dentais/economia
6.
7.
J Inherit Metab Dis ; 30(5): 783-9, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17703370

RESUMO

AIM: This study reports the first evaluation of therapeutic response in Romanian patients with Gaucher disease type I, after therapy with Cerezyme recently became available in our country. PATIENTS AND METHODS: 24 patients (11-50 years) received Cerezyme 20-60 U/kg every two weeks for at least 18 months. Haemoglobin, platelet count, volume of the liver and spleen, plasma chitotriosidase and the severity score were assessed every 6 months; skeletal radiography and osteodensitometry were also monitored. RESULTS: Eleven patients were splenectomized before start of therapy. Eight patients had anaemia (mean haemoglobin 9.4 g/dl) and 14 patients, of whom 13 were without splenectomy, had thrombocytopenia (mean 65,692/mm3). Haemoglobin values normalized after 6 months and the platelet count increased to 147,818/mm3 after 18 months of treatment. Splenomegaly improved (mean 13.8x to 5.6x normal), hepatomegaly improved (mean 1.4x to 1.06x normal), the severity score decreased (mean 15.9 to 8.4), plasma chitotriosidase levels showed a reduction from 40,956 to 11,266 nmol/h per ml plasma. Bone disease improved clinically in all patients; bone radiography and osteodensitometry showed no further disease progress. We observed a mean weight gain of 4.3 kg, an improvement in quality of life, and the absence of therapeutic adverse events. CONCLUSIONS: Enzyme replacement therapy administered for 18 months in Romanian patients with Gaucher disease type I led to a marked improvement in haematological parameters and hepato- and splenomegaly. In the majority of patients we observed no further progress of bone disease; for an improvement in skeletal disease, a longer treatment period is required.


Assuntos
Doença de Gaucher/tratamento farmacológico , Glucosilceramidase/uso terapêutico , Adolescente , Adulto , Anemia/tratamento farmacológico , Anemia/etiologia , Doenças Ósseas/tratamento farmacológico , Doenças Ósseas/etiologia , Criança , Terapia Combinada , Feminino , Seguimentos , Doença de Gaucher/sangue , Doença de Gaucher/complicações , Doença de Gaucher/cirurgia , Glucosilceramidase/efeitos adversos , Hemoglobinas/metabolismo , Hexosaminidases/sangue , Humanos , Hepatopatias/tratamento farmacológico , Hepatopatias/etiologia , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Qualidade de Vida , Proteínas Recombinantes/uso terapêutico , Romênia , Índice de Gravidade de Doença , Esplenectomia , Esplenomegalia/tratamento farmacológico , Esplenomegalia/etiologia , Trombocitopenia/tratamento farmacológico , Trombocitopenia/etiologia , Fatores de Tempo , Resultado do Tratamento , Aumento de Peso/efeitos dos fármacos
8.
J Hosp Infect ; 66(4): 360-8, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17655975

RESUMO

Meticillin-resistant Staphylococcus aureus (MRSA) persists in the hospital environment and conventional cleaning procedures do not necessarily eliminate contamination. A prospective study was conducted on an intensive care unit to establish the level of environmental contamination with MRSA, assess the effectiveness of hydrogen peroxide vapour (HPV) decontamination and determine the rate of environmental recontamination. MRSA was isolated from 11.2% of environmental sites in the three months preceding the use of HPV and epidemiological typing revealed that the types circulating within the environment were similar to those colonising patients. After patient discharge and terminal cleaning using conventional methods, MRSA was isolated from five sites (17.2%). After HPV decontamination but before the readmission of patients, MRSA was not isolated from the environment. Twenty-four hours after readmitting patients, including two colonized with MRSA, the organism was isolated from five sites. The strains were indistinguishable from a strain with which a patient was colonized but were not all confined to the immediate vicinity of the colonized patient. In the eight weeks after the use of HPV, the environment was sampled on a weekly basis and MRSA was isolated from 16.3% sites. Hydrogen peroxide vapour is effective in eliminating bacteria from the environment but the rapid rate of recontamination suggests that it is not an effective means of maintaining low levels of environmental contamination in an open-plan intensive care unit.


Assuntos
Descontaminação/métodos , Desinfetantes/farmacologia , Contaminação de Equipamentos/prevenção & controle , Peróxido de Hidrogênio/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificação , Contagem de Colônia Microbiana , Infecção Hospitalar/prevenção & controle , Humanos , Controle de Infecções/métodos , Unidades de Terapia Intensiva , Resistência a Meticilina/efeitos dos fármacos , Estudos Prospectivos , Staphylococcus aureus/crescimento & desenvolvimento , Volatilização
9.
Br Dent J ; 202(6): E15; discussion 326-7, 2007 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-17299424

RESUMO

OBJECTIVE: The purpose of this ecological study was to investigate the relationship between uptake of orthodontic services and factors that might influence receipt of care at a population level. METHOD: The dental practice board supplied data on claims for courses of active orthodontic treatment from April 2001 to March 2002 for children from the former county of Avon. These data were analysed in relation to deprivation, living in an urban/rural setting and the proportion of the population from a black or minority ethnic group (BME). RESULTS: In Avon, children from deprived and rural areas were significantly less likely to be undergoing an active course of orthodontic treatment. Children from an area with a high proportion BME were significantly more likely to be undergoing treatment. CONCLUSION: This research demonstrates that children from more deprived and rural communities in Avon are less likely to receive orthodontic treatment. This has important policy implications for primary care trusts that have a responsibility to ensure equal access to care for all of their children.


Assuntos
Assistência Odontológica para Crianças/estatística & dados numéricos , Má Oclusão/terapia , Ortodontia Corretiva/estatística & dados numéricos , Adolescente , Criança , Etnicidade/estatística & dados numéricos , Feminino , Humanos , Masculino , Análise de Regressão , População Rural , Fatores Socioeconômicos , População Urbana
10.
Int Dent J ; 56(1): 7-16, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16515007

RESUMO

OBJECTIVE: To examine the provision of dental services by salaried personnel in the countries of Western Europe, together with Australia, Canada and New Zealand, and to weigh the merits of this method against alternatives, namely, capitation and fee for item of service. In light of the findings, to consider the future role of salaried dental services in the National Health Service (NHS) in England. METHOD: Information was gathered from published reports, the World Wide Web and by mailed questionnaire to national chief dental officers or equivalents. RESULTS: Narrative descriptions of service provision in the countries with salaried primary dental care services were compiled. Demographic, macro-economic, workforce, and oral health data for the broader spectrum of Western industrialised countries were tabulated. Examination of the quantitative data showed no strong associations between variables. CONCLUSIONS: Dental services delivered by a salaried workforce can be costly in relation to the volume of clinical activity produced. However, deployment of clinical auxiliary personnel can keep costs down. Salaried services foster a preventive approach to care and are particularly suitable where care is directed towards vulnerable groups within the community. Salaried staff generally receive a lower level of remuneration than private practitioners but usually work in an environment less subject to undue pressures of time.


Assuntos
Atenção à Saúde/economia , Serviços de Saúde Bucal/economia , Países Desenvolvidos , Salários e Benefícios , Odontologia Estatal/economia , Austrália , Canadá , Capitação , Auxiliares de Odontologia , Inglaterra , Europa (Continente) , Planos de Pagamento por Serviço Prestado , Custos de Cuidados de Saúde , Humanos , Internet , Nova Zelândia , Odontologia Preventiva/economia , Prática Privada/economia , Inquéritos e Questionários , Fatores de Tempo , Populações Vulneráveis , Local de Trabalho
11.
Community Dent Health ; 22(2): 86-93, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15984133

RESUMO

OBJECTIVES: To document data on current and past levels of dental decay in British children and compare trends with those in other countries, in Europe in particular. METHOD: Data were abstracted from multiple sources and collated and tabulated. RESULTS: The dental health of the majority of British children has improved dramatically since the early 1970s. Twelve-year-old children now have on average less than one decayed, missing (extracted) or filled tooth. Levels of dental decay in UK children at 5 and 12 years are among the lowest in the world. There are still marked inequalities in the dental decay experience of children between the territorial regions of the UK, high and low socio-economic groups, and regular and symptomatic dental attenders. Many children in areas of deprivation are either not motivated to seek dental treatment or experience barriers in obtaining it. In parallel with improvements in the dental health of the majority of children, the proportion of UK adults who have no natural teeth has fallen from 37% to 12% over the past four decades. Total tooth loss is now confined almost entirely to individuals over 45 years of age. Most of the improvements in children's dental health are attributable to environmental factors, in particular the widespread availability of fluoride containing toothpastes since the 1970s. There are clear benefits from fluoridation of public water supplies over and above those attributable to other factors. CONCLUSIONS: The findings suggest initiatives should be directed to bringing children from deprived backgrounds under the umbrella of dental care. To help alleviate the inequalities in dental health, water fluoridation should be implemented, in urban industrial areas in particular, where levels of dental decay are still unacceptably high.


Assuntos
Cárie Dentária/epidemiologia , Adolescente , Adulto , Criança , Pré-Escolar , Índice CPO , Países Desenvolvidos/estatística & dados numéricos , Europa (Continente)/epidemiologia , Fluoretação , Humanos , Pessoa de Meia-Idade , Prevalência , Classe Social , Reino Unido/epidemiologia
12.
Br Dent J ; 196(12): 761-5; discussion 759, 2004 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-15220982

RESUMO

OBJECTIVES: To determine current demographic details of dental specialist registrars in the UK, to examine their current working patterns and ascertain their future career aspirations. METHODS: A cross-sectional survey, using a self-administered postal questionnaire of all 418 dental specialist registrars (SpRs) in the UK. RESULTS: The response rate was 78%. Of the SpRs who responded 59% were male, the majority were aged under 36, 54% were married and over one third had dependants. Orthodontics had the greatest number of SpRs with 141, followed by maxillofacial surgery (70) and restorative dentistry (52). On completion of training, 80% of SpRs intended to work full time. Significantly more women intended to work part-time. Only a fifth of SpRs said they would consider an academic appointment compared with 54% for specialist practice. Three quarters intended to work partly in the public sector and partly in a private capacity. London was the most popular choice of location for a post in the future. Access to a wide range of clinical work, continuing professional development, autonomy and sociability were the most important factors when considering their future choice of career. CONCLUSION: Changes in the demographic profile of dental specialists and increasing opportunities for providing care within primary care may lead to difficulties in recruitment to academic and hospital posts. Increasing provision of specialist services in the 'high street' might improve access but could lead to inequalities unless these services are commissioned according to the needs of the population.


Assuntos
Especialidades Odontológicas , Adulto , Escolha da Profissão , Estudos Transversais , Feminino , Humanos , Masculino , Padrões de Prática Odontológica , Especialidades Odontológicas/educação , Odontologia Estatal , Inquéritos e Questionários , Reino Unido , Recursos Humanos
13.
Gene Ther ; 10(21): 1841-9, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12960974

RESUMO

Sandhoff disease is a severe inherited neurodegenerative disorder resulting from deficiency of the beta-subunit of hexosaminidases A and B, lysosomal hydrolases involved in the degradation of G(M2) ganglioside and related metabolites. Currently, there is no viable treatment for the disease. Here, we show that adenovirus-mediated transfer of the beta-subunit of beta-hexosaminidase restored Hex A and Hex B activity after infection of Sandhoff fibroblasts. Gene transfer following intracerebral injection in a murine model of Sandhoff disease resulted in near-normal level of enzymatic activity in the entire brain at the different doses tested. The addition of hyperosmotic concentrations of mannitol to the adenoviral vector resulted in an enhancement of vector diffusion in the injected hemisphere. Adenoviral-induced lesions were found in brains injected with a high dose of the vector, but were not detected in brains injected with 100-fold lower doses, even in the presence of mannitol. Our data underline the advantage of the adjunction of mannitol to low doses of the adenoviral vector, allowing a high and diffuse transduction efficiency without viral cytotoxicity.


Assuntos
Adenoviridae/genética , Terapia Genética/métodos , Vetores Genéticos/administração & dosagem , Manitol/administração & dosagem , Doença de Sandhoff/terapia , beta-N-Acetil-Hexosaminidases/genética , Animais , Encéfalo/enzimologia , Difusão , Fibroblastos/enzimologia , Hexosaminidase A , Hexosaminidase B , Injeções , Camundongos , Camundongos Mutantes , Modelos Animais , Doença de Sandhoff/enzimologia , beta-N-Acetil-Hexosaminidases/metabolismo
14.
J Cell Mol Med ; 4(4): 297-302, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-12067465

RESUMO

Inherited resistance to activated protein C has been recognized as a major risk factor for thrombosis. The factor V Leiden mutation, which is detectable by molecular DNA techniques, is responsible for 95% of cases of activated protein C resistance. In our study one patient with venous leg ulcers from a family with a history of thrombosis showed factor V Leiden mutation. Genotypic analysis demonstrated that the patient was homozygous for factor V Leiden. All family members of the index subject showed the same abnormalities. Two were homozygous and 3 were heterozygous for factor V Leiden mutation. The polymerase chain reaction was used to amplify exon 10 of the factor V gene, followed by enzymatic digestion with MnlI for mutation detection. Patients with a family history of thrombosis and factor V Leiden have an increased risk of venous leg ulcers. Screening for factor V Leiden may be indicated in patients with venous leg ulcers and their family members.

15.
Carcinogenesis ; 19(6): 1153-6, 1998 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9667757

RESUMO

This study examined the expression of fibroblast growth factor receptor 2 (FGFR 2) splice variants, IIIb and IIIc, in normal and malignant human oral keratinocytes and in normal oral fibroblasts by RT-PCR using both exon-specific primers and primers common to both FGFR 2 isoforms. Fibroblasts expressed exclusively FGFR 2/IIIc whilst the normal and malignant keratinocytes co-expressed FGFR 2/IIIb and FGFR 2/IIIc. Well-differentiated keratinocytes expressed proportionally more FGFR 2/IIIb than IIIc whereas the poorly-differentiated cells expressed more FGFR 2/IIIc than IIIb. The normal and malignant keratinocytes, but not fibroblasts, expressed an additional amplification product, which consisted of both IIIb and IIIc of FGFR 2 joined by an extra base pair and with the intronic sequence removed. The results indicate that the expression of FGFR 2 isoforms reflects the degree of cellular differentiation in normal and malignant human oral keratinocytes and that receptor complexes of FGFR 2/IIIb and IIIc may regulate ligand-receptor interactions.


Assuntos
Carcinoma de Células Escamosas/patologia , Diferenciação Celular/genética , Neoplasias Bucais/patologia , Receptores Proteína Tirosina Quinases/genética , Receptores de Fatores de Crescimento de Fibroblastos/genética , Carcinoma de Células Escamosas/genética , Éxons , Humanos , Neoplasias Bucais/genética , Reação em Cadeia da Polimerase , Splicing de RNA , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos
16.
J Oral Pathol Med ; 26(7): 327-33, 1997 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9250933

RESUMO

This study examined the mitogenic response to keratinocyte growth factor (KGF) of normal and tumour-derived human oral keratinocytes in which the degree of cellular differentiation was known and in contiguous fibroblast cultures derived from the malignant epithelial cultures. Keratinocytes, but not fibroblasts, were stimulated by KGF, thereby demonstrating epithelial target cell specificity of the ligand. KGF-induced stimulation of the tumour-derived keratinocytes cultured in the absence of the 3T3 fibroblast support broadly correlated with the degree of cellular differentiation; well-differentiated keratinocytes were stimulated more by KGF than their less differentiated counterparts. Malignant oral keratinocytes expressed KGF cell surface receptors (KD 451-709 pM; receptors/cell 2306-13645), but KGF receptor mRNA did not correlate with either KGF-induced mitogenesis or the degree of epithelial cell differentiation. When the tumour-derived keratinocytes were cultured in the presence of 3T3 fibroblasts, the mitogenic response to KGF was comparable to normal epithelial cells. The results suggest that KGF-mediated growth stimulation may not be significant in providing a selective advantage for the growth of malignant keratinocytes.


Assuntos
Fatores de Crescimento de Fibroblastos , Substâncias de Crescimento/farmacologia , Queratinócitos/efeitos dos fármacos , Receptores de Fatores de Crescimento de Fibroblastos , Receptores de Fatores de Crescimento/metabolismo , Células 3T3 , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Northern Blotting , Carcinoma de Células Escamosas/metabolismo , Diferenciação Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Células Cultivadas , Técnicas de Cocultura , Feminino , Fator 10 de Crescimento de Fibroblastos , Fator 7 de Crescimento de Fibroblastos , Fibroblastos/efeitos dos fármacos , Humanos , Queratinócitos/metabolismo , Masculino , Camundongos , Pessoa de Meia-Idade , RNA Mensageiro/análise , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos , Células Tumorais Cultivadas
17.
Hum Mutat ; 9(3): 234-42, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9090526

RESUMO

Metachromatic leukodystrophy (MLD), a lysosomal storage disease caused by the deficiency of arylsulfatase A (ASA), is inherited as an autosomal recessive trait, and its frequency is estimated to be 1 in 40,000 live births. Genomic DNA from 21 MLD patients (14 late-infantile and 7 juvenile cases) was amplified in four overlapping PCR fragments and tested by allele-specific oligonucleotide (ASO) for the two common mutations 459 + 1G-->A and P426L. These mutations were found in only 28.6% of the alleles studied. The remaining alleles were analyzed by chemical mismatch cleavage (CMC) and automatic sequencing. In addition to five previously reported mutations (459 + 1G-->A, A212V, R244C, R390W, P426L), 10 novel mutations were identified: 9 missense mutations (S95N, G119R, D152Y, R244H, S250Y, A314T, R384C, R496H, K367N) and one 8 bp deletion in exon 1, the first mutation reported in this exon. These methods allowed us to identify 76% of the alleles tested. Genotype-phenotype correlations could be established for some of these mutations. These results confirm the heterogeneity of mutations causing MLD and suggest that CMC is a reliable and informative screening method for point mutation detection in the arylsulfatase A gene.


Assuntos
Cerebrosídeo Sulfatase/genética , Leucodistrofia Metacromática/genética , Mutação , Alelos , Cerebrosídeo Sulfatase/análise , Análise Mutacional de DNA , Éxons , Genótipo , Humanos , Hibridização de Ácido Nucleico , Fenótipo , Mutação Puntual/genética , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Deleção de Sequência/genética
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