RESUMEN
Aicardi-Goutières syndrome (AGS) is an autosomal recessive neurological disorder, the clinical and immunological features of which parallel those of congenital viral infection. Here we define the composition of the human ribonuclease H2 enzyme complex and show that AGS can result from mutations in the genes encoding any one of its three subunits. Our findings demonstrate a role for ribonuclease H in human neurological disease and suggest an unanticipated relationship between ribonuclease H2 and the antiviral immune response that warrants further investigation.
Asunto(s)
Trastornos Heredodegenerativos del Sistema Nervioso/enzimología , Trastornos Heredodegenerativos del Sistema Nervioso/genética , Ribonucleasa H/genética , Secuencia de Aminoácidos , Secuencia de Bases , ADN/genética , Encefalitis Viral/congénito , Femenino , Humanos , Masculino , Modelos Moleculares , Datos de Secuencia Molecular , Mutación , Estructura Cuaternaria de Proteína , Subunidades de Proteína , Ribonucleasa H/química , Ribonucleasa H/metabolismo , SíndromeRESUMEN
Functional outcome and provision of care to 82 children (males:females 2.7:1; age range 0 to 16 years) with severe head injury were investigated. The children were admitted to the intensive care units of the Regional Neuroscience Units of the Greater Manchester and Lancashire districts of the North West Region of the UK between 1994 and 1996. A questionnaire was devised based on 12 areas of recovery and data were collected at discharge and 6 weeks, 6 months and 12 months from discharge. Data were collected during home visits and at joint assessment at 12 months with the district consultant community paediatrician (CCP). Early involvement of the CCP enhanced the provision of needs at discharge and 6 weeks after discharge, as did a period of stay in district-level care before discharge home. CCPs received formal notification of the injured child in only 32% of cases by discharge, and 54% of cases by 6 months. Sixty-five per cent of children required early educational support but structured help reached only 55% of these children by the end of the study. Integrated planning between health and education was achieved in about half of the study population. Good physical recovery was achieved by the majority of children but parents said they did not feel prepared for the degree of help which their child still required 12 months after discharge. Children who required anticonvulsants at 12 months' follow-up scored significantly lower on cognitive potential. Psychosocial family functioning deteriorated in a substantial number of families according to parental perception. Prevalence of this perception did not diminish over the study period. Aspects of caregivers' understanding and the child's language deficits, self-care skills, fine and gross motor performance, as well as family, social, and financial consequences were assessed. A dedicated and integrated approach to assessment and provision of care across the domains of hospital, education, and community is discussed.