Mechanisms and brain specific consequences of genomic imprinting in Prader-Willi and Angelman syndromes

Monoallelic gene expression: a repertoire of recurrent themes

“…This regulation appears to be mediated by imprinting centers, which are responsible for the establishment of a differential genomic imprint, the maintenance of this imprint through development, and the ultimate execution of the differential expression programs of the two parental alleles. Thus, in rare cases, Prader–Willi/Angelman's can actually come about through the disruption of the imprinting center itself, which leads to misregulation of the entire imprinted domain (3).…”

“…Imprinting is also of medical significance, because several genetic diseases are associated with defects in imprinted gene expression. Human chromosome 15, for example, contains a large cluster of imprinted genes (3), and deletion of the paternal allele causes Prader–Willi syndrome, a developmental disease characterized by defects in growth control and brain function. Deletion of the maternal allele, on the other hand, brings about Angelman's syndrome, which is a completely different disease associated with severe mental retardation.…”

Genomic imprinting and the expression of affect in Angelman syndrome: what's in the smile?

“…Cortical atrophy, microencephaly and ventricular dilation are evident and related to compromised expression of UBE3A in the neocortex, hippocampus and striatum and Purkinje cells in the cerebellum. UBE3A is thought to play a role in determining axon guidance, neuronal connectivity and degradation of potentially harmful proteins (Schumacher, 2001). Resultant profound or severe intellectual disability is the norm, speech rarely develops and sleep disturbance, hyperactivity, excessive sociability and preference for water play are reported (Miano et al, 2004; Clarke & Marston, 2000; Ishmael, Begleiter, & Butler, 2002).…”

Síndrome de inversión duplicación del cromosoma 15 (INVDUP15) «de novo»: presentación de tres casos clínicos

“…Existen teorías sobre la génesis de la disomía uniparental materna y la invdup (15) por errores de segregación en meiosis I y la ausencia de contribución paterna se explica por un gameto nulisómico o por rescate de una aneuploidía 17,18 , aunque actualmente se considera la posibilidad de un evento tanto pre-como posrecombinación 19 . Por otra parte, la extensión del material genético extra determinada por CGH array y el origen parental del mismo puede ayudar al asesoramiento genético, ya que parece existir una correlación entre las características clínicas y la dosis génica de los genes expresados 20 , muchos de ellos con impronta genómica 21 . Recientemente se han encontrado ocho nuevos locus relacionados con metilación diferencial en el cromosoma 15, lo cual puede ser útil para valorar el grado de expresión génica en estos casos 22 .…”