RESUMEN
In the present study, the cytogenetic and molecular cytogenetic analysis of 90 children with autism and their mothers (18 subjects) was carried out. Chromosome fragility and abnormalities were found in four cases: mos 47,XXX[98]/ 46,XX[2]; 46,XY,r(22)(p11q13); 46,XY,inv(2)(p11.2q13),16qh-; 46Y,fra(X)(q27.3)16qh-. Using C-banding and quantitative fluorescent in situ hybridization (FISH), the significantly increased incidence of heterochromatic region variation was shown in autism as compared to the controls (48 and 16%, respectively). Pericentric 9phqh inversion was not characteristic of the patients with autism whereas heterochromatic variations 1phqh, 9qh+ and 16qh- were more frequent in autism (p<0,05). Basing on the data obtained, a possible role of position effect in autism pathogenesis as well as a potential of heterochromatic region variation analysis for the search of biological markers of autistic spectrum disorders are discussed.
Asunto(s)
Trastorno Autístico/genética , Aberraciones Cromosómicas , Cromosomas Humanos Par 16/genética , Cromosomas Humanos Par 1/genética , Cromosomas Humanos Par 9/genética , ADN/genética , Heterocromatina/genética , Adolescente , Adulto , Niño , Preescolar , Femenino , Estudios de Seguimiento , Marcadores Genéticos , Humanos , Hibridación in Situ , Lactante , Masculino , PronósticoRESUMEN
Rett's syndrome (RTT) is a severe hereditary disorder of the nervous system. MECP2 gene mutations are considered as a primary cause of the disease. In the present study, we have found MECP2 mutations in 33 (84.6%) out of 39 RTT females. We have also studied X-inactivation patterns in 70 girls with RTT. A frequency of skewed X-inactivation was 37% (26 patients), being significantly higher (p < 0.001) than that in the controls. The investigation of inactivated X chromosome origin revealed that about 33% pairs had preferentially the inactivated maternal X chromosome. An abnormal type of chromosome X inactivation was observed in all RTT females. Thus, we conclude that skewed X-inactivation may be considered as a common feature of RTT. There is unambiguous evidence that epigenetic alterations in RTT are associated with MECP2 mutations. MeCP2 protein also appears to be involved in transcriptional regulation of chromosome X genes. RTT in females without MECP2 mutations is related to the epigenetic alterations. We suggest X chromosome inactivation study in RTT females and their mothers to be informative for investigation of genetic processes in RTT girls, even in case MECP2 mutations have not been found. RTT could be considered as an appropriate model for studying epigenetic abnormalities in relation to autistic spectrum disorders.
Asunto(s)
Proteínas Cromosómicas no Histona/genética , Cromosomas Humanos X/genética , Proteínas de Unión al ADN/genética , Proteínas Represoras/genética , Síndrome de Rett/genética , Niño , Análisis Mutacional de ADN , Compensación de Dosificación (Genética) , Femenino , Humanos , Proteína 2 de Unión a Metil-CpG , Madres , Mutación Missense/genética , Linaje , Mutación Puntual/genética , Reacción en Cadena de la Polimerasa , Receptores Androgénicos/genética , Programas InformáticosRESUMEN
Rett syndrome (RTT) is a severe neurodevelopmental disorder caused by mutations in methyl-CpG-binding protein 2 gene (MECP2). We carried out a mutations analysis in Russian cohort of patients with RTT. MECP2 mutations were found in 23 of 28 RTT girls and one boy (82%). Thirteen different types of mutations have been identified: 6 nonsense, 5 missense and 2 deletions in MECP2 gene. In typical RTT form, most frequent mutations were R255X (5 cases) and T158M (4 cases). A boy with classical clinical picture of RTT had R270X mutation. Skewed inactivation of chromosome x has been found in 2 of 27 RTT girls with classical RTT form and "forme fruste". The data obtained imply possible correlations between genotype and phenotype in RTT.
Asunto(s)
Proteínas Cromosómicas no Histona , Proteínas Represoras , Síndrome de Rett/genética , Niño , Preescolar , Cromosomas Humanos X , Codón sin Sentido/genética , Estudios de Cohortes , Análisis Mutacional de ADN , Proteínas de Unión al ADN/genética , Femenino , Genotipo , Humanos , Masculino , Proteína 2 de Unión a Metil-CpG , Fenotipo , Mutación Puntual/genéticaAsunto(s)
Encéfalo/patología , Síndrome de Rett , Encéfalo/anomalías , Preescolar , Aberraciones Cromosómicas/genética , Trastornos de los Cromosomas , ADN Mitocondrial/genética , Diagnóstico Diferencial , Insuficiencia de Crecimiento/complicaciones , Femenino , Humanos , Lactante , Cariotipificación , Masculino , Fenotipo , Mutación Puntual/genética , Síndrome de Rett/complicaciones , Síndrome de Rett/diagnóstico , Síndrome de Rett/genética , Trastorno de Movimiento Estereotipado/complicaciones , Cromosoma X/genéticaRESUMEN
Rett syndrome in 32 children (31 girls and 1 boy) was diagnosed according to International association on Rett syndrome. The phenomenon of the presence of special type of late-replicating chromosome X (type C) was revealed. This phenomenon may be recommended as a diagnostic test for both preclinical periods of development of the disease and in atypical cases of Rett syndrome.
Asunto(s)
Síndrome de Rett/diagnóstico , Cromosoma X , Niño , Preescolar , Sondas de ADN/química , Replicación del ADN , Femenino , Marcadores Genéticos , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Masculino , Linaje , Síndrome de Rett/genética , Síndrome de Rett/metabolismo , Aberraciones Cromosómicas SexualesRESUMEN
Indices of both platelet serotoninergic system and the system of nerve growth factor (NGF) were examined in children with neurofibromatosis (15 patients), polygenic oligophrenia (24 patients) and Rett's syndrome (14 ones). There was an increase of both the level of blood serum autoantibodies (aAB) to NGF and the value of specific binding of 3H-imipramine (Bmax) in platelets of patients with oligophrenia. For this group of patients a significant negative correlation exists between the rate of platelet uptake of serotonin (Vmax value) and the degree of mental retardation (r = -0.425, p < 0.03). Decrease of both Vmax and activity of platelet NGF receptors was revealed in patients with neurofibromatosis. In such patients there was positive correlation between sensitivity of platelet NGF receptors to NGF (during their stimulation by test dose of purified NGF) and the degree of mental retardation (r = 0.697, p < 0.04). In patients with Rett's syndrome a significant increase of activity of platelet NGF receptors to NGF was observed. The conclusion was made on the existence of some general mechanism of intellectual defect development. Autoimmune processes considered to be such mechanism.