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1.
Eur J Clin Microbiol Infect Dis ; 39(6): 1137-1145, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32006177

RESUMO

Urogenital schistosomiasis (UGS) remains common in sub-Saharan African migrants. The aim of the study was to describe UGS cases detected among patients attending primary healthcare consultations in free outpatient clinics in Paris. This retrospective cohort study included all cases of active UGS from 2004 to 2017. Cases were defined by the presence of Schistosoma haematobium typical ova at urine microscopy. Primary care physicians prescribed it on the basis of epidemiological or clinical criteria. Demographic, clinical, biological, and imaging data were retrieved. Active UGS was diagnosed in 105 cases. The sex ratio (F/M) was 3/102 with a median age of 25. Most cases came from West Africa and recently arrived in Europe (median delay, 1 year). Patients under 18 (23%) were more frequent after 2011. Compatible symptoms were reported in 63/104 patients (60%), hematuria being the most frequent (43/104). Urine dipstick detected micro-hematuria in 42/60 patients screened (70%). In 73 cases, urine microscopy was performed from either one, two, or three micturitions on separate days. The rate of positive urine microscopy increased from one (69.2%) to two micturitions (95.4%). All patients except three received praziquantel. Among those who underwent ultrasonography, 30/86 (35%) had abnormalities, 28/30 at the bladder. A step-by-step clinical assessment led to the detection of active UGS: questions on age, location in childhood and hematuria, physical examination, and urine dipstick. A prospective study in primary care is needed for protocol-based management of active UGS to be part of a socio-medical program for migrants.


Assuntos
Esquistossomose Urinária/diagnóstico , Esquistossomose Urinária/epidemiologia , Migrantes , Adolescente , Adulto , África Subsaariana , Instituições de Assistência Ambulatorial/estatística & dados numéricos , Animais , Anti-Helmínticos/uso terapêutico , Feminino , Hematúria/parasitologia , Hematúria/urina , Humanos , Masculino , Pessoa de Meia-Idade , Paris/epidemiologia , Estudos Retrospectivos , Schistosoma haematobium/isolamento & purificação , Esquistossomose Urinária/tratamento farmacológico , Esquistossomose Urinária/urina , Adulto Jovem
2.
Arch Pediatr ; 29(5): 340-346, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35644716

RESUMO

INTRODUCTION: French Guiana is a French overseas territory in South America, marked by poverty and inequalities. Access to different services, including healthcare, is unequal depending on where people live. Several studies showed that among adults, the most precarious individuals had greater incidences of chronic and infectious diseases. Although the median age of the population living in this territory is 25, there is no specific focus on the pediatric population although it is documented that socioeconomic inequalities have an impact on child health. The objective of this scoping review is to shed light on health challenges concerning children living in French Guiana. METHODS: A literature search was performed on PubMed to identify relevant articles, and additional references were added if within the scope of this review. RESULTS: A total of 106 publications were reviewed. Perinatal health issues were linked to a high rate of teenage pregnancies with poor medical follow-up leading to complications such as preterm deliveries and congenital malformations and abnormalities. Infectious diseases were a significant burden with worrisome vaccination coverage figures for some bacterial infections, partly explaining a high mortality rate attributable to infectious diseases. Herbicide poisoning with paraquat was reported in children, and environment-related concerns such as wild animal attacks as well as lead and mercury exposure were reported. Some children living in remote Amerindian communities had a higher suicide rate than in mainland France, and chronic diseases such as sickle cell disease were reported to have more transfusion-related complications. CONCLUSION: Children living in French Guiana have worse pediatric health indicators in comparison with children from mainland France.


Assuntos
Atenção à Saúde , Disparidades nos Níveis de Saúde , Adolescente , Animais , Criança , Feminino , Guiana Francesa/epidemiologia , Humanos , Incidência , Gravidez , Cobertura Vacinal
3.
Infect Dis Now ; 52(4): 193-201, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35483634

RESUMO

Given the number of people leaving the war zone in Ukraine and arriving in France, the French high council for public health (HCSP) has drawn up a number of recommendations. The experts have taken into account the vulnerability of migrant populations, which is exacerbated by (a) promiscuity that increases the risk of exposure to infectious agents; (b) the psychological consequences of conflict, family separation and exile; (c) prevalence in Ukraine of communicable diseases such as (possibly multi-resistant) tuberculosis, HIV and HCV; (d) low vaccination coverage (risk of circulation of poliovirus) and (e) the risk of spreading infectious diseases (Covid-19, measles…). Consequently, experts recommend that priority be given to: (i) Initial (immediate) reception, which will help to provide emergency care and to assess immediate needs (psychological disorders, risk of medication breakdown and risk of infection); (ii) Other priority measures (vaccination catch-up, including vaccination against SARS-CoV-2 and mandatory vaccination for children's entry into school, screening for post-traumatic stress disorder and tuberculosis) must be implemented as soon as feasible. At this stage, it is imperative: To ensure coordination and access to information throughout the country, by providing medico-social support (opening of social rights and access to care); To digitize medical data for the purposes of traceability; To use professional interpreting and/or health facilitators, or else, if necessary, digital translation tools. (iii) Finally, experts stress the need for vigilance in terms of management, conservation of social rights and continuity of care after the initial period, and organization of a "health rendezvous" within four months of a migrant's entering the country.


Assuntos
COVID-19 , Migrantes , COVID-19/epidemiologia , Criança , Humanos , Saúde Pública , SARS-CoV-2 , Ucrânia/epidemiologia
4.
Infect Dis Now ; 52(7): 389-395, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36064101

RESUMO

OBJECTIVES: Patients lost to follow-up and treatment failure in tuberculosis disease (TB) are major public health issues. In the absence of appropriate treatment, approximately 70 % of smear-positive patients will die within 10 years of disease progression. This study, conducted in the French region with the highest incidence, aimed to assess tuberculosis treatment outcomes and its determinants. PATIENTS AND METHODS: A prospective, multicenter cohort study (CO1TB) of adults and children treated for TB was conducted in four hospitals in the North of Paris. Treatment outcome at 1 year and associated socioeconomic and clinical factors were studied by multivariate logistic regression. RESULTS: Among 145 TB cases included from May 2018 to January 2020, patients were mainly born abroad and most lived in difficult socioeconomic conditions. During treatment, 25/145 (17 %) patients experienced adverse effects, which were not significantly associated with discontinuation of treatment (p = 0.99). At 1 year, 114 (78 %) had completed treatments, 26 (19 %) were lost to follow-up, three (2.1 %) were still being treated and two (1.4 %) had died. In the multivariate analysis, a history of TB was significantly associated with unfavorable treatment outcome (aOR = 5.3, 95 %CI (1.5;18.6) and a trend towards significance (p < 0.2) was observed among patients aged under 24 years (aOR = 2.9, 95 %-CI 0.95;8.5). CONCLUSION: In this precarious population, socioeconomic conditions were not found to be associated with unfavorable treatment outcome, whereas history of tuberculosis and young age played a role. Increased monitoring is thus required for these patients.


Assuntos
Infecções por HIV , Tuberculose , Adulto , Criança , Humanos , Idoso , Antituberculosos/uso terapêutico , Estudos de Coortes , Estudos Prospectivos , Infecções por HIV/tratamento farmacológico , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia , Resultado do Tratamento , França/epidemiologia
5.
J Viral Hepat ; 18(7): e358-65, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21692948

RESUMO

Elastometry has demonstrated good accuracy, but little is known about its reproducibility. The aim of this study was to assess the intra- and inter-operator reproducibility of liver stiffness measurement among hepatitis C virus (HCV)-infected patients in Egypt. The study was conducted among HCV-infected patients referred for treatment evaluation in two hepatitis treatment centres of Cairo. Two operators took liver stiffness measurement two times per patient the same day. Intra- and inter-reproducibility were estimated by different methods: Bland and Altman graphics, variation coefficient, intraclass correlation coefficient and Kappa coefficient; 7.1 kPa was used as the threshold of significant (≥F2) fibrosis whenever needed. Fifty-eight patients were included in the study, and 216 measurements were taken. Failure rate was 7% and associated with overweight. For a value of 7.1 kPa, the inter-operator 95% limits of agreement were estimated at ±2.88 kPa. Intra- and inter-operator coefficients of variation ranged between 11% and 15%, intraclass correlation coefficients [95% confidence interval] between 0.94 [0.86-0.97] and 0.97 [0.95-0.99], and Kappa coefficients between 0.65 [0.44-0.88] and 0.92 [0.81-1.00]. The reliability of liver stiffness measurement is questionable when considering the decision to initiate antiviral therapy because of the percentage of discordance between measurements is notable, especially in the intermediate fibrosis stages.


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Hepatite C/complicações , Cirrose Hepática/patologia , Fígado/patologia , Adulto , Egito , Elasticidade , Feminino , Humanos , Cirrose Hepática/etiologia , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
6.
Infect Dis Now ; 51(4): 319-333, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33681861

RESUMO

At the end of December 2019, China notified the World Health Organization about a viral pneumonia epidemic soon to be named COVID-19, of which the infectious agent, SARS-CoV-2, was rapidly identified. Less than one year later, published phase 3 clinical trials underlined the effectiveness of vaccines utilizing hitherto unusual technology consisting in injection of the messenger RNA (m-RNA) of a viral protein. In the meantime, numerous clinical trials had failed to identify a maximally effective antiviral treatment, and mass vaccination came to be considered as the strategy most likely to put an end to the pandemic. The objective of this text is to address and hopefully answer the questions being put forward by healthcare professionals on the different anti-SARS-CoV-2 vaccines as regards their development, their modes of action, their effectiveness, their limits, and their utilization in different situations; we are proposing a report on both today's state of knowledge, and the 14 February 2021 recommendations of the French health authorities.


Assuntos
Vacinas contra COVID-19 , COVID-19/prevenção & controle , Humanos
7.
Int J Tuberc Lung Dis ; 25(11): 903-910, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34686232

RESUMO

SETTING: Migrants to Europe face a disproportionate burden of infections, including TB, yet little is known about the approach taken by primary and secondary care providers to screening and treatment. We therefore explored policy and practice relating to screening of active TB and latent TB infection (LTBI) in France.METHODS: We conducted an online national survey of French primary and secondary care physicians regarding their practices in relation to TB/LTBI screening among migrants.RESULTS: 367 physicians responded to the questionnaire among which 195 (53.1%) were primary care physicians, 126 (34.3%) were TB specialists in secondary care, and 46 (12.5%) other physicians; 303 (85.5%) were involved daily in the care of migrants. Most respondents recommended systematic TB screening with chest X-ray for migrants from medium and high-incidence countries (71.9%). Primary care physicians were less likely to offer screening than physicians in other settings (aOR 0.21, 95% CI 0.09-0.48). 220 (61.8%) offered LTBI screening for children (<15 years) and 34.0% for all migrants from high incidence countries.CONCLUSION: Improving awareness on TB screening is a critical next step to improve health outcomes in migrant groups and meet regional targets for tackling TB.


Assuntos
Tuberculose Latente , Migrantes , Criança , Europa (Continente) , França/epidemiologia , Humanos , Tuberculose Latente/diagnóstico , Tuberculose Latente/epidemiologia , Programas de Rastreamento
8.
Vaccine ; 39(25): 3315-3318, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34011464

RESUMO

COVID-19 vaccine hesitancy is frequent and can constitute a barrier to the dissemination of vaccines once they are available. Unequal access to vaccines may also contribute to socioeconomic inequalities with regard to COVID-19. We studied vaccine hesitancy among persons living in homeless shelters in France between May and June 2020 (n = 235). Overall, 40.9% of study participants reported vaccine hesitancy, which is comparable to general population trends in France. In multivariate regression models, factors associated with vaccine hesitancy are: being a woman (OR = 2.55; 95% CI 1.40-4.74), living with a partner (OR = 2.48, 95% CI 1.17-5.41), no legal residence in France (OR = 0.51, 95% CI 0.27-0.92), and health literacy (OR = 0.38, 95% CI 0.21, 0.68). Our results suggest that trends in vaccine hesitancy and associated factors are similar among homeless persons as in the general population. Dissemination of information on vaccine risks and benefits needs to be adapted to persons who experience severe disadvantage.


Assuntos
COVID-19 , Pessoas Mal Alojadas , Vacinas , Vacinas contra COVID-19 , Feminino , França/epidemiologia , Humanos , SARS-CoV-2
9.
Bull Soc Pathol Exot ; 113(1): 42-51, 2020.
Artigo em Francês | MEDLINE | ID: mdl-32881441

RESUMO

The issue of catching up vaccines among children and adult migrants is of concern in France. Migrants do not represent a homogeneous population, but a majority of them are insufficiently vaccinated on the basis of the French vaccination schedule that includes more vaccine than those of their countries of origin. Among migrants, people in precarious situations or belonging to certain social groups have poorer immunization coverage, are exposed to a delay in the implementation of their catch-up and are at higher risk of vaccine-preventable infectious diseases. Epidemic situations of vaccine-preventable diseases have been observed in France, accelerating the awareness of the need to implement catch-up vaccination programs and highlighting the difficulties to implement this catch-up in people who have, for the most, already received vaccinations in their countries of origin but have no vaccine proof. Different catch-up strategies are possible with or without pre- or post-vaccination serologies and were the subject of recommendations co-developed by the French High Authority in Health (HAS) and the French Infectious Disease Society (SPILF).


La problématique du rattrapage vaccinal chez les enfants et adultes migrants s'installant en France est un enjeu de santé publique. Les migrants ne représentent pas une population homogène, mais une majorité d'entre eux sont insuffisamment vaccinés au regard du calendrier vaccinal français qui est plus exigeant que ceux des pays d'origine. Au sein des populations migrantes, les personnes en situation de précarité ou appartenant à certains groupes sociaux sont plus souvent insuffisamment vaccinées, sont exposées à un retard de la mise en œuvre de son rattrapage, alors qu'elles sont surexposées au risque de maladies infectieuses à prévention vaccinale comme la rougeole ou la varicelle. Des situations épidémiques de maladies à prévention vaccinale ont été observées en France, accélérant la prise de conscience de la nécessité de mettre en place des programmes de rattrapage vaccinal. Leur mise en œuvre est confrontée à la problématique des modalités pratiques de ce rattrapage chez des personnes ayant pour la grande majorité déjà reçu des vaccinations dans leur pays d'origine, mais n'ayant pas de trace de ces dernières. Différentes stratégies de rattrapage sont possibles avec ou sans recours à des sérologies préou postvaccinales notamment et ont fait l'objet de discussions et de l'élaboration de recommandations sous l'égide de la Haute Autorité de santé (HAS) et de la Société de pathologie infectieuse de langue française (SPILF).


Assuntos
Migrantes , Vacinação/estatística & dados numéricos , França , Humanos
10.
Genomics ; 91(1): 52-60, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18060737

RESUMO

Familial hypertrophic cardiomyopathy (FHC) is an autosomal dominant disease characterized by left ventricular hypertrophy (LVH) predominantly affecting the interventricular septum. Cardiac myosin-binding protein C (cMyBP-C) mutations are common causes of FHC. Gene expression profiling was performed in left ventricles of 9-week-old wild-type mice, heterozygous cMyBP-C KO mice displaying asymmetric septal hypertrophy, and homozygous mice developing eccentric LVH. Knocking out one or two cMyBP-C genes leads primarily to gene expression changes indicating an increased energy demand, activation of the JNK and p38 parts of the MAPK pathway and deactivation of the ERK part, and induction of apoptosis. Altered gene expression for processes related to cardiac structure, contractile proteins, and protein turnover was also identified. Many of the changes were more pronounced in the homozygous KO mice. These alterations point to physiological and pathological adaptations in the prehypertrophic heterozygous KO mice and the hypertrophic homozygous mice.


Assuntos
Cardiomiopatia Hipertrófica Familiar/metabolismo , Proteínas de Transporte/metabolismo , Transtornos Cromossômicos/metabolismo , Regulação da Expressão Gênica , Hipertrofia Ventricular Esquerda/metabolismo , Miocárdio/metabolismo , Animais , Apoptose/genética , Cardiomiopatia Hipertrófica Familiar/genética , Cardiomiopatia Hipertrófica Familiar/patologia , Proteínas de Transporte/genética , Transtornos Cromossômicos/genética , Transtornos Cromossômicos/patologia , MAP Quinases Reguladas por Sinal Extracelular , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/genética , Heterozigoto , Homozigoto , Hipertrofia Ventricular Esquerda/genética , Hipertrofia Ventricular Esquerda/patologia , MAP Quinase Quinase 4/genética , MAP Quinase Quinase 4/metabolismo , Sistema de Sinalização das MAP Quinases/genética , Camundongos , Camundongos Knockout , Miocárdio/patologia , Análise de Sequência com Séries de Oligonucleotídeos , Septo Interventricular/metabolismo , Septo Interventricular/patologia , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
12.
Med Mal Infect ; 46(6): 318-21, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27235009

RESUMO

OBJECTIVE: To evaluate the efficacy of amikacin on sputum conversion during initial sputum smear positive tuberculosis treatment. MATERIAL AND METHODS: Single-center observational cohort study (2012-2013) evaluating time to sputum smear conversion with standard treatment (ST) versus standard treatment+amikacin (IV 15mg/kg/day) for seven days (STamK). RESULTS: Forty-five patients were included. Median time to smear negative samples was 26.5 days (14-56) for the 30 (66.7%) patients included in the ST group and 48 days (19.5-69.5) for the 15 patients (33.3%) included in the STamK group (P=0.76). Time to negative culture was only known for 27 patients (61.4%): 47.5 days (26-58) for 18 patients in the ST group and 40 days (14-77) for nine patients in the STamK group. CONCLUSION: Despite our small sample size, the addition of amikacin in active tuberculosis treatment did not seem to impact time to smear conversion or period of contagiousness.


Assuntos
Amicacina/uso terapêutico , Antituberculosos/uso terapêutico , Tuberculose Pulmonar/tratamento farmacológico , Adulto , Amicacina/administração & dosagem , Antituberculosos/administração & dosagem , Carga Bacteriana , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Isolamento de Pacientes , Escarro/microbiologia , Fatores de Tempo
13.
Neurology ; 57(7): 1319-22, 2001 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-11591858

RESUMO

The authors report a case of congenital muscular dystrophy with mild nonprogressive muscle weakness, white matter hypodensity, and absence of the laminin alpha2 chain in muscle fibers with two antibodies, but not with four others. They identified mutations in LAMA2, which explain the partial laminin alpha2 deficiency. Analysis of this case and two others allows us to refine the epitopes of two of the commercial antibodies, and illustrate the importance of using antibodies directed against different domains of the protein.


Assuntos
Laminina/genética , Distrofias Musculares/genética , Anticorpos Monoclonais/imunologia , Especificidade de Anticorpos , Biópsia , Criança , Pré-Escolar , Epitopos/imunologia , Humanos , Imuno-Histoquímica , Laminina/deficiência , Laminina/imunologia , Masculino , Músculo Esquelético/patologia , Distrofias Musculares/congênito , Distrofias Musculares/patologia , Mutação , Fenótipo
14.
Neuromuscul Disord ; 10(1): 59-62, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10677866

RESUMO

The dystrophia muscularis dy2J/dy2J mouse is an animal model for one form of human congenital muscular dystrophy. A point mutation in the gene coding for the laminin-2 alpha 2 chain leads to the expression of a truncated, partially functional protein. We developed a simple assay for the detection of the dy2J allele, which contains a new NdeI restriction site. Genomic DNA was prepared from animals of known status and amplified by PCR. The digestion of the PCR product with the restriction enzyme resulted in characteristic profiles. Then, this technique was used to identify heterozygous mice among unaffected animals of unknown status. Subsequently, the heterozygous genotype of these mice was confirmed by the birth of dystrophic offspring after mating. This technique allows the detection of the dy2J allele in heterozygous and homozygous animals at any age.


Assuntos
Heterozigoto , Homozigoto , Distrofia Muscular Animal/genética , Reação em Cadeia da Polimerase , Alelos , Animais , Sequência de Bases/genética , Enzimas de Restrição do DNA , Genótipo , Laminina/genética , Camundongos , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Mutação Puntual/genética
15.
Neuromuscul Disord ; 10(8): 548-52, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11053680

RESUMO

We report a case of congenital muscular dystrophy with secondary merosin deficiency, structural involvement of the central nervous system and mental retardation in an 8-year-old girl from a consanguineous family. She had early-onset hypotonia, generalized muscle wasting, with weakness especially of the neck muscles, joint contractures, mental retardation and high creatine kinase. Muscle biopsy showed dystrophic changes with partial deficiency of the laminin alpha(2) chain. Cranial magnetic resonance imaging revealed multiple small cysts in the cerebellum, without cerebral cortical dysplasia or white matter changes. The laminin alpha(2) chain (6q2), Fukuyama type congenital muscular dystrophy (9q31-q33) and muscle-eye-brain disease (1p32-p34) loci were all excluded by linkage analysis. We suggest that this case represents a new entity in the nosology of congenital muscular dystrophy.


Assuntos
Cistos do Sistema Nervoso Central/genética , Cerebelo/anormalidades , Deficiência Intelectual/genética , Laminina/deficiência , Laminina/genética , Distrofias Musculares/complicações , Distrofias Musculares/genética , Cistos do Sistema Nervoso Central/patologia , Cistos do Sistema Nervoso Central/fisiopatologia , Cerebelo/patologia , Cerebelo/fisiopatologia , Criança , Mapeamento Cromossômico , Feminino , Ligação Genética/genética , Humanos , Deficiência Intelectual/patologia , Deficiência Intelectual/fisiopatologia , Laminina/metabolismo , Imageamento por Ressonância Magnética , Proteínas de Membrana , Linhagem , Proteínas/genética , Regulação para Cima/genética
16.
Neuromuscul Disord ; 8(3-4): 169-74, 1998 May.
Artigo em Inglês | MEDLINE | ID: mdl-9631397

RESUMO

The evidence of severe structural brain abnormalities in association with severe mental retardation is characteristic in congenital muscular dystrophy (CMD) forms other than the 'classical' form. However, it seems that the nosology of CMD is not complete yet, as we have clinical, immunohistochemical and genetic data suggesting that there are other unclassified forms. Here we report two CMD siblings from a consanguineous family with partial merosin-deficiency in muscle biopsies, severe mental retardation and normal MRI of the brain. The disease was not linked to the LAMA2 gene (6q22-23) or to Fukuyama congenital muscular dystrophy (FCMD) (9q31-33). To our knowledge, such an association may constitute a new entity within the broad clinical spectrum of CMD.


Assuntos
Encéfalo/patologia , Deficiência Intelectual/complicações , Laminina/deficiência , Imageamento por Ressonância Magnética , Distrofias Musculares/complicações , Distrofias Musculares/metabolismo , Criança , Genótipo , Humanos , Imuno-Histoquímica , Laminina/metabolismo , Masculino , Distrofias Musculares/congênito , Distrofias Musculares/genética , Linhagem , Valores de Referência
17.
Neuromuscul Disord ; 7(3): 180-6, 1997 May.
Artigo em Inglês | MEDLINE | ID: mdl-9185182

RESUMO

Congenital muscular dystrophies (CMD) are a clinically and genetically heterogeneous group of muscle disorders, with autosomal recessive inheritance. Absence of the laminin alpha 2 chain in the skeletal muscle of patients with classical CMD has permitted the identification of a subgroup, referred to as 'merosin-deficient CMD or laminin alpha 2 chain deficient CMD'. We first identified a nonsense and a splice site mutation in laminin alpha 2 gene (LAMA2) (Glu1241 stop, 4573-2A-->T). We report here new mutations: nonsense mutations (Glu210stop, Trp2316stop) and 1- and 2-bp deletions (2418 delta C, 6968 delta TA), which result in truncation of the protein either in the short arm domains or in the C terminal globular domain and complete merosin deficiency. Another subgroup, referred to as 'partially-deficient in laminin alpha 2 chain' has been identified recently, and a LAMA2 missense mutation (Cys996Arg) has been shown to cause this partial deficiency. The laminin alpha 2 chain, together with the beta 1 or beta 2 and gamma 1 chains forms either laminin-2 (alpha 2-beta 1-gamma 1) or laminin-4 (alpha 2-beta 2-gamma 1). The LAMA2 mutations induce the formation of abnormal laminins which probably dramatically disturb the assembly and stability of the laminin network, one of the major components of the extracellular matrix in skeletal muscle. We report also the first prenatal diagnosis performed by direct mutation analysis.


Assuntos
Laminina/genética , Distrofias Musculares/diagnóstico , Distrofias Musculares/genética , Diagnóstico Pré-Natal , Mapeamento Cromossômico , Análise Mutacional de DNA , Saúde da Família , Feminino , Humanos , Laminina/deficiência , Masculino , Distrofias Musculares/congênito , Mutação , Linhagem
18.
Med Mal Infect ; 44(1): 42-4, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24274977
19.
Biochem Biophys Res Commun ; 260(2): 357-64, 1999 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-10403775

RESUMO

We have determined the structure and the exon size pattern of the human integrin alpha7 subunit gene (ITGA7), which has been shown to be affected in a form of congenital myopathy. The gene is composed of at least 27 exons spanning a region of about 22.5 kb. The sequence of all exon/intron boundaries was determined and conforms to the GT/AG splicing consensus. We investigated the different splicing forms previously described in human and rodents. The major cytoplasmic variants alpha7A and alpha7B, which are developmentally regulated and tissue specific, were identified in human tissues, as well as the extracellular isoforms X1 and X2. The recently described D variant was detected in adult tissues by RT-PCR but not the C variant. We localized ITGA7 on chromosome 12q13 by high-resolution radiation hybrid mapping between D12S312 and D12S90 and identified a new CA-repeat microsatellite in intron 1.


Assuntos
Antígenos CD/genética , Cadeias alfa de Integrinas , Músculo Esquelético/metabolismo , Miocárdio/metabolismo , RNA Mensageiro/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Mapeamento Cromossômico , Cromossomos Humanos Par 12 , DNA Complementar , Repetições de Dinucleotídeos , Éxons , Humanos , Íntrons , Camundongos , Dados de Sequência Molecular , Splicing de RNA , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Homologia de Sequência de Aminoácidos
20.
Ann Neurol ; 47(6): 811-6, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10852549

RESUMO

It is becoming evident that clinical phenotypes associated with partial laminin alpha2 chain deficiency are variable. We recently observed a 29-year-old man with leukoencephalopathy and vacuolar myopathy resembling inclusion body myositis. Laminin alpha2 immunohistochemical analysis showed reduction of the protein on muscle fiber surfaces. Molecular analysis revealed two novel compound heterozygous mutations in the LAMA2 gene. This is the first report linking a mutation in the LaMA2 gene with leukoencephalopathy and inclusion body-like myositis.


Assuntos
Encefalopatias/genética , Encefalopatias/patologia , Laminina/deficiência , Laminina/genética , Fibras Musculares Esqueléticas/patologia , Miosite/genética , Miosite/patologia , Adulto , Sequência de Aminoácidos , Sequência de Bases , Diagnóstico Diferencial , Éxons , Feminino , Heterozigoto , Humanos , Imuno-Histoquímica , Laminina/análise , Masculino , Miosite de Corpos de Inclusão/patologia , Linhagem , Vacúolos/patologia , Vacúolos/ultraestrutura
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