RESUMEN
Gilles de la Tourette syndrome is a complex neuropsychiatric disorder with a strong genetic basis. We identified a male patient with Tourette syndrome-like tics and an apparently balanced de novo translocation [46,XY,t(2;7)(p24.2;q31)]. Further analysis using array comparative genomic hybridisation (CGH) revealed a cryptic deletion at 7q31.1-7q31.2. Breakpoints disrupting this region have been reported in one isolated and one familial case of Tourette syndrome. In our case, IMMP2L, a gene coding for a human homologue of the yeast inner mitochondrial membrane peptidase subunit 2, was disrupted by the breakpoint on 7q31.1, with deletion of exons 1-3 of the gene. The IMMP2L gene has previously been proposed as a candidate gene for Tourette syndrome, and our case provides further evidence of its possible role in the pathogenesis. The deleted region (7q31.1-7q31.2) of 7.2 Mb of genomic DNA also encompasses numerous genes, including FOXP2, associated with verbal dyspraxia, and the CFTR gene.
Asunto(s)
Puntos de Rotura del Cromosoma , Cromosomas Humanos Par 7/genética , ADN/análisis , Endopeptidasas/genética , Tics/genética , Síndrome de Tourette , Apraxias/genética , Apraxias/fisiopatología , Cromosomas Humanos Par 7/ultraestructura , Hibridación Genómica Comparativa , Regulador de Conductancia de Transmembrana de Fibrosis Quística/deficiencia , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Endopeptidasas/metabolismo , Exones , Factores de Transcripción Forkhead/deficiencia , Factores de Transcripción Forkhead/genética , Humanos , Hibridación Fluorescente in Situ , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos , Linaje , Eliminación de Secuencia , Tics/fisiopatología , Síndrome de Tourette/genética , Síndrome de Tourette/fisiopatología , Translocación GenéticaRESUMEN
Genomic microarrays have been implemented in the diagnosis of patients with unexplained mental retardation. This method, although revolutionizing cytogenetics, is still limited to the detection of rare de novo copy number variants (CNVs). Genome-wide single nucleotide polymorphism (SNP) microarrays provide high-resolution genotype as well as CNV information in a single experiment. We hypothesize that the widespread use of these microarray platforms can be exploited to greatly improve our understanding of the genetic causes of mental retardation and many other common disorders, while already providing a robust platform for routine diagnostics. Here we report a detailed validation of Affymetrix 500k SNP microarrays for the detection of CNVs associated to mental retardation. After this validation we applied the same platform in a multicenter study to test a total of 120 patients with unexplained mental retardation and their parents. Rare de novo CNVs were identified in 15% of cases, showing the importance of this approach in daily clinical practice. In addition, much more genomic variation was observed in these patients as well as their parents. We provide all of these data for the scientific community to jointly enhance our understanding of these genomic variants and their potential role in this common disorder.
