RESUMO
AIMS: The first wave of the COVID-19 pandemic generated "risks" and uncertainties as well as organizational changes among French perinatal caregivers. Our study aimed to investigate the psychosocial impact of the first wave on this population. METHOD: Our participants (N=565) were invited to answer an online questionnaire that included questions on various indices of health and quality of life at work (e.g., ProQoL, perceived stress) and other questions on the impact of the pandemic on work organization. An open-ended question was designed to identify the participants' three most frequently perceived preoccupations with regard to the health situation. RESULTS: In addition to highlighting the multifactorial nature of participants' preoccupations, our results illustrated the effect of professional status and type of motherhood on the different indices of health and quality of life at work. When it was found that the pandemic had an impact on work organization and on teams, lower health and quality of work life scores were recorded. On the other hand, when positive impacts on organization were reported, mainly in terms of reduced work intensity, they were associated with higher health and quality of work life scores. CONCLUSION: We explain this last result as either one actual effect of the pandemic on work organization, or as a phenomenon of cognitive rationalization.
Assuntos
COVID-19 , Qualidade de Vida , Adaptação Psicológica , COVID-19/epidemiologia , Cuidadores , Humanos , Pandemias , Qualidade de Vida/psicologiaRESUMO
Melioidosis is an infectious disease caused by Burkholderia pseudomallei, a bacterium endemic in Southeast Asia and northern Australia. In New Caledonia, sporadic cases were first described in 2005; since then, more cases have been identified. To improve our understanding of melioidosis epidemiology in New Caledonia, we compared the local cases and B. pseudomallei isolates with those from endemic areas. Nineteen melioidosis cases have been diagnosed in New Caledonia since 1999, mostly severe and with frequent bacteraemia, leading to three (16%) fatalities. All but one occurred in the North Province. Besides sporadic cases caused by non-clonal strains, we also identified a hotspot of transmission related to a clonal group of B. pseudomallei that is phylogenetically related to Australian strains.
Assuntos
Bacteriemia/epidemiologia , Bacteriemia/microbiologia , Burkholderia pseudomallei/fisiologia , Melioidose/epidemiologia , Melioidose/microbiologia , Bacteriemia/transmissão , Técnicas de Tipagem Bacteriana , Burkholderia pseudomallei/genética , DNA Bacteriano/genética , DNA Bacteriano/metabolismo , Feminino , Humanos , Masculino , Melioidose/transmissão , Pessoa de Meia-Idade , Tipagem de Sequências Multilocus , Nova Caledônia/epidemiologia , Filogenia , Análise de Sequência de DNARESUMO
Using data from a regional medical follow-up network database of preterm infants born with gestational age (GA) <33 weeks, we found that low GA and deprived socioeconomic neighborhoods increased incidence of infection-related hospitalization during the first year of life. Respiratory tract infections rates were higher in extremely preterm infants.
Assuntos
Hospitalização , Recém-Nascido Prematuro , Recém-Nascido , Lactente , Humanos , Idade Gestacional , Fatores Socioeconômicos , HospitaisRESUMO
We aimed to describe the real-life role of high-flow nasal cannula (HFNC) for bronchiolitis in infants under 3 months of age admitted to three general pediatric departments during the 2017-2018 epidemic period. We retrospectively assessed the clinical severity (Wang score) for every 24-h period of treatment (H0-H24 and H24-H48) according to the initiated medical care (HFNC, oxygen via nasal cannula, or supportive treatments only), the child's discomfort (EDIN score), and transfer to the pediatric intensive care unit (PICU). A total of 138 infants were included: 47±53 days old, 4661±851.9 g, 70 boys (50.7%), 58 with hypoxemia (42%), Wang score of 6.67±2.58, 110 (79.7%) staying for 48 consecutive hours in the same ward. During the H0-H24 period, only patients treated with HFNC had a statistically significant decrease in the severity score (n=21/110; -2 points, P=0.002) and an improvement in the discomfort score (n=15/63; -3.8 points, P<0.0001). There was no difference between groups during the H24-H48 period. The rate of admission to the PICU was 2.9% for patients treated for at least 24 h with HFNC (n=34/138, 44% with oxygen) versus 16.3% for the others (P=0.033). Early use of HFNC improves both clinical status and discomfort in infants younger than 3 months admitted for moderately severe bronchiolitis, whatever their oxygen status.
Assuntos
Bronquiolite/terapia , Oxigenoterapia/métodos , Doença Aguda , Bronquiolite/diagnóstico , Cânula , Feminino , Departamentos Hospitalares , Hospitalização , Humanos , Lactente , Recém-Nascido , Masculino , Oxigenoterapia/instrumentação , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
INTRODUCTION AND OBJECTIVE: Information on the spectrum and frequencies of pediatric neurological presentations to emergency departments is vital to optimize quality of care. The objective of this study was to determine the incidence of pediatric neurological emergencies and to analyze the impact of specialist neurological advice in emergency care. PATIENTS AND METHODS: We performed a retrospective descriptive study of pediatric emergency room visits for neurological reasons at the Timone University Hospital in Marseille over a 6-month period (from October 2017 to March 2018). RESULTS: Of the 14,572 emergencies analyzed, 370 (2.5%) were for neurological conditions. These were most commonly seizures (56.7% of cases), headache (19.7%), and motor or sensory deficits (5.1%). The most frequent diagnosis was epileptic seizure (30%), followed by febrile seizure (26.1%) and migraine (15%). Around two in every five patients (37.6%) required hospitalization. Neurological emergencies requiring critical care occurred at a frequency of about one per month (1.6% of cases). A pediatric neurologist was consulted in 37.3% of cases, resulting in a modification of the diagnosis or treatment in 66% of these referrals. CONCLUSION: The results of this study suggest that a formal referral system between the emergency department and pediatric neurologists would be useful.
Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Doenças do Sistema Nervoso/epidemiologia , Neurologistas , Encaminhamento e Consulta/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , Emergências , Serviço Hospitalar de Emergência/organização & administração , Feminino , França/epidemiologia , Hospitais Universitários/organização & administração , Hospitais Universitários/estatística & dados numéricos , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/terapia , Encaminhamento e Consulta/organização & administração , Estudos RetrospectivosRESUMO
In spite of the frequency of sexual dysfunction in schizophrenic patients and antipsychotic-treated schizophrenic patients, few studies have been performed. The relationship of schizophrenia to sexual pathology is variable and complex, and of course different between men and women. Few evaluation methods have been proposed or validated. Antipsychotics may improve some aspects of sexual behaviour in schizophrenic patients. However, sexual dysfunction is also a possible side effect of these drugs. The evaluation of antipsychotics is often restricted to prolactin measurement, the relationship with sexual disorders of which has not been fully established. Preliminary data suggest that the capacity to induce sexual disorders differs from one antipsychotic to another. The available data on the mechanisms of sexual dysfunction, the pharmacological profile and the sexual effects of classical neuroleptics (haloperidol and thioridazine) and second generation antipsychotics available in France (amisulpride, clozapine, risperidone, olanzapine) are reviewed.
Assuntos
Antipsicóticos/efeitos adversos , Esquizofrenia/tratamento farmacológico , Psicologia do Esquizofrênico , Comportamento Sexual/efeitos dos fármacos , Disfunções Sexuais Fisiológicas/induzido quimicamente , Antipsicóticos/uso terapêutico , Estudos Transversais , Disfunção Erétil/induzido quimicamente , Disfunção Erétil/epidemiologia , Feminino , França , Humanos , Masculino , Esquizofrenia/epidemiologia , Disfunções Sexuais Fisiológicas/diagnóstico , Disfunções Sexuais Fisiológicas/epidemiologia , Disfunções Sexuais Fisiológicas/psicologiaRESUMO
INTRODUCTION: Even if there are HAS (French National Health Authority) guidelines on shaken baby syndrome, many other child abuse situations are not included in these recommendations. The aim of this study was to invent the complementary exams in cases of child abuse in France and compare the practice to existing guidelines. MATERIAL AND METHODS: This was a multicenter study by email to 128 French hospitals (35 university hospitals and 93 general hospitals) that receives children in emergency and hospitalization settings. Three child abuse clinical situations were included in a clinical case multiple-choice format concerning the further explorations. We described the main results and evaluated their adherence to the HAS protocol for case 1. RESULTS: Of 128 hospitals surveyed, 104 responded, for an 81 % response rate, which corresponded to 274 doctors. Analysis of the results showed great heterogeneity in practices. The majority of physicians (99 %) performed systematic explorations in the situation of physical abuse, while only 27 % undertook such exams in situations of serious neglect. The situation of sexual abuse was the most consensual in terms of diagnostic tests for the detection of sexually transmitted diseases, but other types of associated abuse were not sought. In the first case, the HAS guidelines were respected in less than half of the cases for all complementary exams except the eye fundus exam. Abdominal imaging was insufficiently performed (40 % of cases). Examinations that were not indicated were still prescribed. Moreover, siblings under 2 years of age were examined in only one-third of cases (n=88/274; 32 %). Practices were not influenced by the age of the child. CONCLUSION: This study illustrates the heterogeneity in the use of complementary exams in cases of child abuse in France. Common protocols throughout the country would be useful, standardizing the most relevant exams for potential medical-legal issues, and facilitating exchanges concerning practices between different centers.
Assuntos
Maus-Tratos Infantis , Fidelidade a Diretrizes , Padrões de Prática Médica/estatística & dados numéricos , Criança , França , Humanos , Guias de Prática Clínica como AssuntoRESUMO
Our study aims to provide a comprehensive view of the endocrine features in Kennedy's disease (KD). Twenty-two men with KD underwent detailed endocrine investigations. Clinical signs of partial androgen resistance were present in more than 80% of the patients, with gynecomastia being the most prominent. Gynecomastia was postpubertal but appeared before muscular weakness in most cases. Thirteen patients had alteration of testicular exocrine function. Hormonal profile of partial androgen resistance was present in 86% of the patients, with an elevated testosterone level in 68%. Androgen insensitivity seems to appear later in life in KD, similar to the development of neurological signs. Although we confirm the previously reported correlation between the CAG repeat length and the early onset of the neurological disease, we describe a significant correlation between repeat length and the age of onset of gynecomastia as well as biological indexes of androgen insensitivity. This is supported by numerous in vitro data correlating variations in the CAG tract with androgen receptor activity; the longer the CAG repeats, the weaker the receptor transactivation. Ours is the first study to show such a clear and prominent pattern of androgen insensitivity in KD. In clinical practice, KD patients are often misdiagnosed as having amyotrophic lateral sclerosis. Careful examination of the endocrine component could avoid such a deleterious misdiagnosis.
Assuntos
Androgênios/metabolismo , Atrofia Muscular Espinal/genética , Atrofia Muscular Espinal/metabolismo , Receptores Androgênicos/genética , Adulto , Idoso , Atrofia , Glicemia , Colesterol/sangue , Estudos de Coortes , Estradiol/sangue , Genótipo , Ginecomastia/genética , Ginecomastia/metabolismo , Ginecomastia/patologia , Humanos , Hormônio Luteinizante/sangue , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/genética , Debilidade Muscular/metabolismo , Debilidade Muscular/patologia , Atrofia Muscular Espinal/patologia , Fenótipo , Receptores Androgênicos/metabolismo , Testículo/patologia , Testosterona/sangue , Repetições de TrinucleotídeosRESUMO
Anti-psychotic medications are an important therapeutic option for many individuals with schizophrenia. Recently, a growing interest has been observed on weight gain, which is now a well-known adverse effect of many anti-psychotics. As obesity is frequently a comorbid condition with schizophrenia, patients with schizophrenia are inherently at increased risk of developing obesity-related conditions such as cardiovascular disease and type 2 diabetes. The consequences of excessive weight gain (obesity) associated with anti-psychotic drugs are likely to include adverse effects on health, social burden and poor compliance or even discontinuation of therapy by the patients. In this article, we focus on different aspects of weight gain induced by anti-psychotics. This review comprises the following sections: (i) the pharmacological basis of anti-psychotic-induced weight gain and metabolic effects with a review of all anti-psychotics that can be used in patients with schizophrenia; (ii) the clinical impact of the body weight gain (morbidity, psychatric consequences, mortality); (iii) the management of obesity (identification of risk factors including pharmacogenetics, diet, behavioural therapies, pharmacological approach). An understanding of these aspects is important for those who prescribe anti-psychotics in order to provide the patient the best therapeutic management.
Assuntos
Antipsicóticos/efeitos adversos , Obesidade/induzido quimicamente , Esquizofrenia/tratamento farmacológico , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/prevenção & controle , Humanos , Obesidade/prevenção & controleRESUMO
Charcot-Marie-Tooth disease, type 1A (CMT1A) is caused in most cases by a 1.5 Mb duplication on chromosome 17p11.2 arising after unequal crossing-over between repeated sequences called CMT1A-REPs, flanking the 1.5 Mb unit. A 3.2 kb recombination hot spot has been defined, resulting in a junction fragment between EcoRI (distal CMT1A-REP) and SacI (proximal CMT1A-REP). This was further reduced to a 1.7kb EcoRI-NsiI fragment, and recently to a 731 bp hot spot region within this fragment. We describe the CMT1A-REPs-based PCR method used to identify CMT1A duplications and report on a family case in which a 29-year-old pregnant woman requested prenatal diagnosis for two successive pregnancies because her husband was affected with CMT1A. Our method enabled us to characterise the duplication in both foetuses and demonstrate that it arose from a rare recombination event taking place outside the 1.7 kb region. Since our approach is simple and enables the entire set of duplications occurring after recombination in the enlarged 3.2kb region including the hot spot to be detected, we suggest it might be considered for use in primary screening for pre- and postnatal diagnosis of CMT1A.
Assuntos
Doença de Charcot-Marie-Tooth/genética , Cromossomos Humanos Par 17 , Doenças Fetais/genética , Duplicação Gênica , Doença de Charcot-Marie-Tooth/diagnóstico , Doença de Charcot-Marie-Tooth/embriologia , Mapeamento Cromossômico , Feminino , Doenças Fetais/diagnóstico , Humanos , Repetições de Microssatélites/genética , Reação em Cadeia da Polimerase/métodos , Gravidez , Diagnóstico Pré-Natal , Recombinação GenéticaRESUMO
Hereditary neuralgic amyotrophy (HNA) is an autosomal disease characterized by painful episodes of brachial palsy. The presence of tomacula in some patients suggested that HNA might be genetically related to hereditary neuropathy with liability to pressure palsies (HNPP), caused by point mutations in the PMP22 gene or deletion of the region containing this gene. In a clinical, electrophysiologic, and molecular study of two families with HNA, we show that the PMP22 gene is not deleted, duplicated, or mutated in HNA and that the disease is not linked to any other gene in the HNPP deleted region. We conclude that HNA and HNPP are distinct genetic entities.
Assuntos
Neurite do Plexo Braquial/fisiopatologia , Proteínas da Mielina/genética , Doenças do Sistema Nervoso Periférico/fisiopatologia , Adolescente , Adulto , Neurite do Plexo Braquial/classificação , Neurite do Plexo Braquial/genética , Criança , Cromossomos Humanos Par 17 , Feminino , Deleção de Genes , Triagem de Portadores Genéticos , Ligação Genética , Genótipo , Humanos , Masculino , Linhagem , Doenças do Sistema Nervoso Periférico/classificação , Doenças do Sistema Nervoso Periférico/genética , Mutação Puntual , Polimorfismo de Fragmento de Restrição , PressãoRESUMO
Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disease characterized by recurrent episodes of acute nerve palsies. We performed a clinical, electrophysiologic, and molecular study of 13 French families with HNPP associated with a chromosome 17p11.2 deletion in 36 individuals. There were electrophysiologic abnormalities in all symptomatic (n = 28) and asymptomatic (n = 8) deletion carriers, even in childhood. Bilateral delayed distal motor latency of the median nerve at the wrist, reduced sensory velocity in the palm-wrist segment, and delayed distal motor latency or reduced motor velocity in the peroneal nerve was diagnostic in at-risk relatives. This large series confirms the reliability of molecular analysis combined with a simplified electrophysiologic examination for the diagnosis of HNPP associated with 17p11.2 deletion.
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 17 , Neuropatia Hereditária Motora e Sensorial/genética , Adolescente , Adulto , Idoso , Sequência de Bases , Criança , Pré-Escolar , Feminino , Neuropatia Hereditária Motora e Sensorial/fisiopatologia , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Condução Nervosa/fisiologia , LinhagemRESUMO
We present clinical, neuropsychological, and neuropathologic data on a large pedigree including 34 subjects with early-onset progressive dementia. The mean (+/- SD) age at onset was 46 +/- 3.5 years and the mean age at death 52.6 +/- 5.7 years. Twelve patients were clinically diagnosed as having probable Alzheimer's disease (AD) according to the NINCDS-ADRDA criteria. Neuropsychological evaluation, performed at a moderate stage of the disease, was available in six subjects and showed a classic pattern of cognitive deficit. Myoclonus and extrapyramidal signs were common, and seizures were present in all affected subjects. There were neuropathologic changes typical of AD in two brains. A significant lod score of 5.48 was observed at a recombination fraction of theta = 0.0 with the genetic marker D14S43, thereby establishing that the responsible gene was located on chromosome 14q24.3. These results suggest that epilepsy could represent a particular feature in AD families linked to chromosome 14q.
Assuntos
Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Encéfalo/patologia , Cromossomos Humanos Par 14 , Idade de Início , Doença de Alzheimer/fisiopatologia , Mapeamento Cromossômico , DNA/sangue , Feminino , Ligação Genética , Marcadores Genéticos , Humanos , Leucócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Emaranhados Neurofibrilares/patologia , Testes Neuropsicológicos , Linhagem , Reação em Cadeia da Polimerase , Valores de Referência , Caracteres Sexuais , Fatores SexuaisRESUMO
OBJECTIVE: To study the clinical and electrophysiologic features of a large series of carriers of the 17p11.2 deletion. BACKGROUND: The 17p11.2 deletion is associated in most patients with recurrent acute nerve palsies, which is the typical presentation of hereditary neuropathy with liability to pressure palsies (HNPP). Nevertheless, a few other phenotypes have been reported. METHODS: On the basis of clinical and electrophysiologic data, the authors conducted a retrospective study of 99 individuals with the 17p11.2 deletion referred to their neurogenetic department between 1993 and 1997. RESULTS: In addition to the typical presentation of HNPP, they describe five other phenotypes in 15 patients: recurrent positional short-term sensory symptoms, progressive mononeuropathy, Charcot-Marie-Tooth disease-like polyneuropathy, chronic sensory polyneuropathy, and chronic inflammatory demyelinating polyneuropathy-like, recurrent subacute polyneuropathy; and 14 asymptomatic patients. In all the deletion carriers, regardless of their phenotype and by the second decade, the authors found a characteristic, multifocal electrophysiologic neuropathy consisting of a diffuse increase in distal motor latencies contrasting with normal or moderately reduced motor nerve conduction velocities, a diffuse reduction in sensory nerve action potential, and multiple focal slowing of nerve conduction at the usual sites of entrapment. The key diagnostic criterion is a bilateral slowing of sensory and motor nerve conduction at the carpal tunnel with at least one abnormal parameter for motor conduction in one peroneal nerve. CONCLUSION: The authors confirm the clinical phenotypic heterogeneity of the 17p11.2 deletion and suggest that electrophysiologic examination is a reliable tool for screening suspected HNPP patients in its various clinical presentations.
Assuntos
Cromossomos Humanos Par 17/genética , Deleção de Genes , Neuropatia Hereditária Motora e Sensorial/genética , Neuropatia Hereditária Motora e Sensorial/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Pessoa de Meia-Idade , Condução Nervosa/fisiologiaRESUMO
OBJECTIVE: To relate X-linked Charcot-Marie-Tooth disease (CMTX) phenotypes to gender and type of neuropathy by the study of a large series of CMTX patients with proven Cx32 point mutations. BACKGROUND: CMTX is an X-linked form of Charcot-Marie-Tooth disease, caused by mutations in the connexin 32 gene. Males are usually more severely affected and have slower nerve conduction velocities than females. METHODS: Forty-eight patients from 10 families with Cx32 mutations were examined clinically and electrophysiologically. Mutations were characterized in index cases by automatic sequencing and detected in at-risk individuals by polymerase chain reaction (PCR)-restriction or single strand conformation polymorphism (SSCP) analysis. Two patients from different families had light and electron microscopy examination of a sural nerve biopsy. RESULTS: Males (n = 21) were more severely affected than females (n = 27), although six of the females were severely disabled. In the majority of males, the median motor nerve conduction velocity (MNCV) was between 30 and 40 m/s, whereas in females it ranged from 30 to normal values. Two children with mutation, a 6-year-old boy and a 7-year-old girl, were normal clinically and electrophysiologically. In most patients, the amplitude of motor nerve compound muscle action potentials (CMAP) was reduced in all nerves tested. MNCV was reduced as a function of the degree of axonal loss. A significant correlation was found between the decrease in CMAP amplitude and MNCV in the median, ulnar, and peroneal nerves. Sural nerve biopsies in one patient with a missense and one with a nonsense mutation both showed axonal neuropathy. CONCLUSION: Electrophysiologic and histologic findings support primary axonal neuropathy in CMTX with Cx32 mutations. Clinical and electrophysiologic data in males with different missense mutations in the of Cx32 gene differed significantly. Furthermore, males with a nonsense mutation (Arg22Stop) had earlier onset and a more severe phenotype than males with missense mutations.
Assuntos
Doença de Charcot-Marie-Tooth/genética , Doença de Charcot-Marie-Tooth/fisiopatologia , Conexinas/genética , Mutação Puntual , Cromossomo X , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Doença de Charcot-Marie-Tooth/patologia , Criança , Eletrofisiologia , Saúde da Família , Feminino , Ligação Genética , Genótipo , Humanos , Masculino , Nervo Mediano/fisiologia , Pessoa de Meia-Idade , Condução Nervosa/fisiologia , Linhagem , Nervo Fibular/fisiologia , Fenótipo , Nervo Sural/patologia , Nervo Ulnar/fisiologia , Proteína beta-1 de Junções ComunicantesRESUMO
The 17p11.2 duplication and Connexin 32 (Cx32) mutations are the most frequent gene mutations responsible for Charcot-Marie-Tooth diseases. We classified 282 Charcot-Marie-Tooth families according to the median motor nerve conduction velocity of the index patient and the mode of inheritance, and screened them for 17p11.2 duplication and Cx32 mutations. Forty-seven percent of the Charcot-Marie-Tooth families had median motor nerve conduction velocity under 30 m/s (group 1), 15% between 30 and 40 m/s (group 2), and 28% over 40 m/s (group 3). Spinal Charcot-Marie-Tooth (group 4) was observed in 7% of the families. Modes of inheritance were not similarly represented among the different groups. The 17p11.2 duplication was detected in index patients of group 1 only, and accounted for 83% of the familial cases and 36% of the isolated cases. In contrast, 21 Cx32 mutations were detected to variable degrees in groups 1-3, but were most numerous by far in dominant families of group 2 (44%). This systematic approach was taken to estimate the frequency of 17p11.2 duplication and Cx32 mutations in the different Charcot-Marie-Tooth subgroups, in order to propose a practical strategy for molecular analysis.
Assuntos
Doença de Charcot-Marie-Tooth/diagnóstico , Doença de Charcot-Marie-Tooth/genética , Cromossomos Humanos Par 17 , Conexinas/genética , Genes Duplicados , Adulto , Criança , Saúde da Família , Feminino , Testes Genéticos , Humanos , Masculino , Neurônios Motores/fisiologia , Condução Nervosa , Proteína beta-1 de Junções ComunicantesRESUMO
The D14S43 marker is closely linked to the major gene for early onset autosomal dominant Alzheimer's disease on chromosome 14. Allelic frequencies at the D14S43 locus were compared in 113 familial and isolated cases of early onset Alzheimer's disease (< 60 years of age at onset) (EOAD) and 109 unaffected individuals of the same geographic origin. Allele 7 was significantly (P = 0.033) more frequent in type 1 EOAD patients (13.2%), defined by the presence of at least another first degree relative with EOAD, than in controls (4.1%). Since an autosomal dominant gene is probably responsible for type 1 patients, allelic association may reflect linkage disequilibrium at the D14S43 locus. This would mean that some patients share a common ancestral mutation. However, since multiple tests were carried out, this result must be interpreted with caution, and needs confirmation in an independent sample.
Assuntos
Alelos , Doença de Alzheimer/genética , Cromossomos Humanos Par 14/genética , Marcadores Genéticos , Adulto , Idade de Início , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genes Dominantes , Ligação Genética , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Polimorfismo GenéticoRESUMO
Recently several reports have extended the apolipoprotein E (APOE) epsilon 4 association found in late-onset Alzheimer's disease (LOAD) patients to early-onset (EO) AD patients. We have studied this question in a large population of 119 EOAD patients (onset < or = 60 years) in which family history was carefully assessed and in 109 controls. We show that the APOE epsilon 4 allele frequency is increased only in the subset of patients who belong to families where LOAD secondary cases are present. Our sampling scheme permits us to demonstrate that for an individual, bearing at least one epsilon 4 allele increases both the risk of AD before age 60 and the probability of belonging to a family with late-onset affected subjects. Our results suggest that a subset of EOAD cases shares a common determinism with LOAD cases.
Assuntos
Doença de Alzheimer/epidemiologia , Doença de Alzheimer/genética , Apolipoproteínas E/genética , Adulto , Idade de Início , Alelos , Apolipoproteína E4 , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The SOX10 transcription factor is involved in development of neural crest derivatives and fate determination in glial cells. SOX10 mutations have been found in patients with intestinal aganglionosis and depigmentation with deafness (Waardenburg-Hirschsprung). Associated neurological signs have been reported in some cases, including a patient exhibiting a central and peripheral myelin deficiency. Therefore, we screened for SOX10 mutations in a large cohort of patients with peripheral and central myelin disorders. 56 were affected by classical demyelinating Charcot-Marie-Tooth disease without identified mutations in the genes encoding PNS myelin proteins (PMP22, P0), connexin 32 and the zinc-finger transcription factor, EGR2. 88 patients with undetermined leukodystrophy were selected from a large European prospective study. Associated clinical, magnetic resonance imaging and electrophysiological signs were consistent with a defect in CNS myelination in 83 and with an active degeneration of the CNS myelin in 5. No abnormalities in the proteolipid protein gene (PLP) were found. The absence of SOX100 mutation in this large cohort of patients suggests that this gene is not frequently involved in peripheral or central inherited myelin disorders.