[Chromosomal causes that produce mental retardation: chromosome disorders that can be diagnosed in the patient]. / Causas cromosomicas que originan el retraso mental: alteraciones cromosomicas diagnosticables en el paciente.

INTRODUCTION: In all the aetiological studies carried out on idiopathic mental retardation (MR), chromosomal abnormalities are the factor that makes the most significant contribution. The alterations are more frequent when severe MR is accompanied by a dysmorphic phenotype, but can also be found in subjects with mild MR and with few signs of dysmorphism. DEVELOPMENT: This work reports on new genes and critical regions in syndromes with microdeletion, such as Wolf-Hirschhorn, Smith-Magenis and Sotos--which must be taken into account in the genetic diagnosis--and new microduplications like 15q11-q13, which is associated to a behavioural phenotype of autism. The application of new molecular techniques, such as fluorescent in situ hybridisation (FISH) with multiple telomere probes, MLPA (multiplex ligation-dependent probe amplification) and array-CGH (microarray based on compared genomic hybridisation), have shown the important role played by subtelomeric and interstitial rearrangements in the aetiology of MR. Subtelomeric alterations contribute to between 5 and 7% of cases of idiopathic MR, the higher proportion corresponding to deletions, one of the most common of which is deletion 1p36. Studies that evaluate the global genome in idiopathic MR detect from 7% to 20% of cases with anomalies, the interstitial type being more frequent than the subtelomeric kind. CONCLUSIONS: The application of new technologies to idiopathic MR opens up a promising new field for the diagnosis of new syndromes with submicroscopic alterations, so that a prognosis can be determined, treatment can be improved and the risk of relapse can be defined.

Causas cromosómicas que originan el retraso mental: alteraciones cromosómicas diagnosticables en el paciente / Chromosomal causes that produce mental retardation: chromosome disorders that can be diagnosed in the patient

Introducción. En todos los estudios etiológicos de retrasomental (RM) idiopático, las anomalías cromosómicas son el factorque contribuye más significativamente. Las alteraciones son más frecuentescuando el RM grave se acompaña de un fenotipo dismórfico,pero pueden encontrarse también en sujetos con RM leve y conescasos signos dismórficos. Desarrollo. Se describen nuevos genes yregiones críticas de síndromes con microdeleción:Wolf-Hirschhorn,Smith-Magenis y Sotos –que deben tenerse en cuenta para el diagnósticogenético–, y nuevas microduplicaciones como la 15q11-q13,que se asocia a un fenotipo conductual de autismo. La aplicación delas nuevas técnicas moleculares como la hibridación in situ fluorescente(FISH) con multisondas multitelómero, MLPA (multiplex ligation-dependent probe amplification) y array-CGH (microarray basadoen la hibridación genómica comparada), ha puesto de manifiestola gran relevancia que tienen las reorganizaciones subteloméricase intersticiales en la etiología del RM. Las alteraciones subteloméricascontribuyen en un 5-7% de los casos con RM idiopático; lamayor proporción corresponde a las deleciones; una de las más comuneses la deleción 1p36. Los estudios que valoran el genoma globalen el RM idiopático detectan desde un 7 a un 20% de casos conanomalías, y son las intersticiales más frecuentes que las subteloméricas.Conclusiones. La aplicación de las nuevas tecnologías alRM idiopático abre un campo muy esperanzador para el diagnósticode nuevos síndromes con alteraciones submicroscópicas, a fin deestablecer un pronóstico, mejorar el tratamiento y definir el riesgode recurrencia

In all the aetiological studies carried out on idiopathic mental retardation (MR), chromosomalabnormalities are the factor that makes the most significant contribution. The alterations are more frequent when severe MR isaccompanied by a dysmorphic phenotype, but can also be found in subjects with mild MR and with few signs of dysmorphism.Development. This work reports on new genes and critical regions in syndromes with microdeletion, such as Wolf-Hirschhorn,Smith-Magenis and Sotos –which must be taken into account in the genetic diagnosis– and new microduplications like 15q11-q13,which is associated to a behavioural phenotype of autism. The application of new molecular techniques, such as fluorescent insitu hybridisation (FISH) with multiple telomere probes, MLPA (multiplex ligation-dependent probe amplification) and array-CGH (microarray based on compared genomic hybridisation), have shown the important role played by subtelomeric andinterstitial rearrangements in the aetiology of MR. Subtelomeric alterations contribute to between 5 and 7% of cases ofidiopathic MR, the higher proportion corresponding to deletions, one of the most common of which is deletion 1p36. Studiesthat evaluate the global genome in idiopathic MR detect from 7% to 20% of cases with anomalies, the interstitial type beingmore frequent than the subtelomeric kind. Conclusions. The application of new technologies to idiopathic MR opens up apromising new field for the diagnosis of new syndromes with submicroscopic alterations, so that a prognosis can be determined,treatment can be improved and the risk of relapse can be defined