RESUMO
AIMS: The pathogenesis of spontaneous cervical artery dissection remains unknown. We examined the association between different polymorphisms frequently found in young patients with cryptogenic stroke [methylenetetrahydrofolate reductase (MTHFR) C677T, factor II (prothrombin) G20210A, factor V G1691A (Leiden), nitric oxide synthase 3 (NOS3) intron 4 VNTR, and apolipoprotein E (APOE) epsilon4 gene] in patients with a cerebral infarct caused by spontaneous cervical artery dissection. METHODS: Forty-eight patients (27 males) and 96 matching control subjects were recruited. Clinical history, including cardiovascular risk factors, was assessed in all subjects. Genotypes were determined by a polymerase chain reaction with and without a restriction fragment length polymorphism. The genotypes and allele frequencies of the five genetic variants studied were compared between spontaneous cervical artery dissection cases and controls. We also incorporated our data into a meta-analysis of the MTHFR/C677T variant. RESULTS: Of 48 patients with spontaneous cervical artery dissection (28 vertebral and 20 carotid), the mean age of the patients was 36.6 +/- SD 9.9 years. There were no significant associations between the alleles of the five genetic polymorphisms studied and spontaneous cervical artery dissection. In the meta-analysis of the MTHFR/C677T variant, a total of 564 individuals (231 cases and 333 controls) were analysed; no significant association was observed. CONCLUSIONS: The results from this exploratory case-control study show the lack of an association between MTHFR, factor II G20210A, factor V G1691A, NOS3, intron 4 VNTR, and APOE epsilon4 gene polymorphisms and the development of spontaneous cervical artery dissection. Our findings contribute towards a better understanding of the genetic risk factors associated with spontaneous cervical artery dissection.
Assuntos
Apolipoproteínas E/genética , Fator V/genética , Predisposição Genética para Doença , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Óxido Nítrico Sintase Tipo III/genética , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , Dissecação da Artéria Vertebral/genética , Adulto , Demografia , Feminino , Genótipo , Humanos , Íntrons/genética , Masculino , Pessoa de Meia-Idade , Repetições Minissatélites/genética , Falha de Tratamento , Resultado do Tratamento , Dissecação da Artéria Vertebral/enzimologiaRESUMO
BACKGROUND: Juvenile myoclonic epilepsy (JME) accounts for 3 to 12% of all epilepsies. In 2004, the GENESS Consortium demonstrated four missense mutations in Myoclonin1/EFHC1 of chromosome 6p12.1 segregating in 20% of Hispanic families with JME. OBJECTIVE: To examine what percentage of consecutive JME clinic cases have mutations in Myoclonin1/EFHC1. METHODS: We screened 44 consecutive patients from Mexico and Honduras and 67 patients from Japan using heteroduplex analysis and direct sequencing. RESULTS: We found five novel mutations in transcripts A and B of Myoclonin1/EFHC1. Two novel heterozygous missense mutations (c.755C>A and c.1523C>G) in transcript A occurred in both a singleton from Mexico and another singleton from Japan. A deletion/frameshift (C.789del.AV264fsx280) in transcript B was present in a mother and daughter from Mexico. A nonsense mutation (c.829C>T) in transcript B segregated in four clinically and seven epileptiform-EEG affected members of a large Honduran family. The same nonsense mutation (c.829C>T) occurred as a de novo mutation in a sporadic case. Finally, we found a three-base deletion (-364--362del.GAT) in the promoter region in a family from Japan. CONCLUSION: Nine percent of consecutive juvenile myoclonic epilepsy cases from Mexico and Honduras clinics and 3% of clinic patients from Japan carry mutations in Myoclonin1/EFCH1. These results represent the highest number and percentage of mutations found for a juvenile myoclonic epilepsy causing gene of any population group.
Assuntos
Proteínas de Ligação ao Cálcio/genética , Saúde da Família , Mutação , Epilepsia Mioclônica Juvenil/genética , Canais de Cloro CLC-2 , Canais de Cloreto/genética , Análise Mutacional de DNA/métodos , Feminino , Genótipo , Honduras/epidemiologia , Humanos , Japão , Masculino , México/epidemiologia , Epilepsia Mioclônica Juvenil/epidemiologia , Fenótipo , Regiões Promotoras Genéticas , Receptores de GABA-A/genéticaRESUMO
We investigated the influence of dehydration-rehydration vesicles (DRV) phospholipid composition and the addition of other components on human recombinant epidermal growth factor (hrEGF) encapsulation efficiency and its release from liposomes. Encapsulation of EGF into DRV composed of phosphatidylcholine with different unsaturation levels was around 20-35%. The best result was obtained with dipalmitoyl phosphatidylcholine: cholesterol (DPPC:Ch) liposomes (35%) corresponding to the lowest hrEGF release during one month of storage. Even with this phospholipid composition, modification of the DRV procedure by including an extrusion step did not improve hrEGF encapsulation efficiency, rendering less stable particles. The inclusion of recombinant P64k from Neisseria meningitidis (rP64k), as such or conjugated to hrEGF, decreased the encapsulation efficiency of the latter protein into DRV or freeze and thaw multilamellar vesicles (FATMLV). The hrEGF release from liposomes could be related to the interaction between this polypeptide and the bilayer, as evidenced by increased carboxyfluorescein release from hrEGF-DRV; less susceptibility to fluorescence quenching by acrylamide in the presence of liposomes; and a measurable decrease of phospholipid phase transition Delta enthalpy (DeltaH). DRV comprising saturated phospholipids (DPPC:Ch or distearoyl phosphatidylcholine [DSPC]:Ch) and containing the conjugate EGF-P64k induced a more efficient immune response against hrEGF than unsaturated phospholipid and alum in terms of total IgG, IgG(2a), and IgG(2b) subclasses and the ability of antibody to inhibit the interaction of the EGF receptor with hrEGF.
Assuntos
Fator de Crescimento Epidérmico/metabolismo , Sistema Imunitário , Fosfolipídeos/química , Animais , Proteínas de Bactérias/metabolismo , Varredura Diferencial de Calorimetria/métodos , Dessecação , Fluoresceínas/metabolismo , Humanos , Imunoglobulina G/química , Bicamadas Lipídicas/química , Lipossomos/química , Lipossomos/metabolismo , Camundongos , Neisseria meningitidis/metabolismo , TermodinâmicaRESUMO
Amongst idiopathic generalized epilepsies, juvenile myoclonic epilepsy (JME) is the most common, accounting for 12% to 30% of all epilepsies in the Western world. Classic JME consists of awakening myoclonias, grand mal convulsions and EEG 4 to 6 Hz polyspike waves that appear in adolescence. Probands and affected family members do not have pyknoleptic 3Hz spike and wave absences. However, in 10 to 30% of patients, rare or spanioleptic polyspike wave absences appear. In 1988,1995,1996,we mapped classic JME to a 7 cM locus in chromosome 6p12 11, called EJM1, using families from Los Angeles and Belize. In 2001,we studied one large family from Belize and 21 new families from Los Angeles and Mexico Cities, aided by a BAC/PAC based physical map and 6 new dinucleotide repeats, to narrow EJM1 to an interval between D6S272 and D6S1573. In 2002, we found myoclonin, the putative gene for typical JME in 6p12. At the congress, we will reveal the identity of the myoclonin gene, its putative function and discuss the significance of this discovery in the JME population at large.
Assuntos
Cromossomos Humanos Par 6 , Epilepsia Mioclônica Juvenil/genética , Belize , California , Eletroencefalografia , Genótipo , Humanos , México , Epilepsia Mioclônica Juvenil/diagnóstico , Epilepsia Mioclônica Juvenil/fisiopatologia , FenótipoRESUMO
We investigated the allele distribution of the polymorphic (CAG)n repeat in the IT15 gene in 96 normal subjects from the Mexican population and 83 unrelated patients with Huntington's disease. Our results show that the size distributions of normal and affected alleles do not overlap. Normal alleles range from 13 to 32 triplets, with 18 being the most frequent allele, while HD alleles contain 37 to 76 repeats with 42 being the most frequent. One allele in the range of intermediate alleles was found (32 repeats) in a normal subject. The juvenile onset cases in this study are associated with an expansion greater than 49 repeats. In the available parent-offspring pairs, paternal alleles show instability with an expansion of 28 repeats in one case.
Assuntos
Doença de Huntington/genética , Repetições de Trinucleotídeos , Adolescente , Adulto , Idade de Início , Idoso , Alelos , Criança , Humanos , México , Pessoa de Meia-IdadeRESUMO
Fifty-eight, at-risk subjects were studied. 81% of the group wished to know whether they had inherited Huntington's disease, even though only 79% would undergo testing. The subjects reported a favorable attitude toward a probable positive result in 81% of cases. Nevertheless, 52% reported they would become depressed, and a small group referred suicidal ideation as response to a probable positive result. Regarding genetic counseling, 59% reported that an at-risk person should not have children, although this increased to 82% if the person knew with certainty that they would develop the disease. Prenatal testing was favored in 74%, and less than half would be willing to have an abortion. Genetic counseling must be insisted upon, the selection of at-risk subjects must be carefully made, and the characteristics of the Mexican population must be taken into account.
Assuntos
Atitude Frente a Saúde , Doença de Huntington/diagnóstico , Doença de Huntington/genética , Adulto , Saúde da Família , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Fatores de RiscoRESUMO
The objective of this study is to investigate the type, importance, and incidence of hereditary diseases in patients at the National Institute of Neurology and Neurosurgery in Mexico City. A review of 6,258 files indicated that hereditary diseases represent an important problem for the Institute. Of the diseases with the highest incidences, hereditary factors have an important role in seven (epilepsy, depression, facial palsy, schizophrenia, mental retardation, migraine, and Parkinson's disease). Diseases of known monogenic etiology represent 1.5% of all the cases.
Assuntos
Encefalopatias/genética , Transtornos Neurocognitivos/genética , Adolescente , Adulto , Encefalopatias/epidemiologia , Criança , Pré-Escolar , Aberrações Cromossômicas/genética , Transtornos Cromossômicos , Estudos Transversais , Feminino , Humanos , Incidência , Lactente , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Transtornos Neurocognitivos/epidemiologiaRESUMO
La distrofia miotónica es una enfermedad multisistémica que se manifesta entre la segunda y tercera década de la vida y se hereda en forma autosómica dominante con elevada penetrancia y expresividad variable pudiendo algunos individuos afectados pasar desapercibidos. El objeto de este trabajo es estudiar 21 pacientes con distrofia miotónica pertenecientes a 18 familias para conocer en esta muestra la edad de inicio, características clínicas, variabilidad en su expresión y problemas que se presentan para dar consejo genético. De los 21 pacientes 14 fueron de sexo masculino y 7 femenino. La edad promedio de inicio de la enfermedad fue de 23.4 años. El sítoma más común fue debilidad muscular. A la exploración física los hallazgos más frecuentes fueron miotonía, atrofia muscular, facies característica y calvicie frontal. El estudio oftalmológico reveló alteraciones en cristalino en el 95% de los pacientes. El estudio psicológico se realizó en 14 pacientes y mostró un C.I. normal en 71.4% y anormal en 28.6%. Una de las pacientes presentó las complicaciones obstétricas comunes de la enfermedad. Encontramos en esta muestra que la edad de inicio y manifestacicones clínicas en los pacientes y sus familiares son muy variables, siendo difícil en ocasiones determinar si una persona es o no heterocigoto. Según Bundey et al un individuo en riesgo asintomático que a los 30 años tiene una electromiografía y examen oftalmológico normal pero tiene familiares con inicio del padecimiento después de los 20 años todavía riesgo de 1 en 4 de haber heredado el padecimiento