Analisi molecolare di geni coinvolti nello spettro fenotipico Angelman-Rett

Within mental retardation, the clinical phenotypes of Rett syndrome and Angelman syndrome have been known and described for a long time. The molecular basis of both these pathologies have been identified: alterations of the MECP2 gene are detected in 80% of the Rett cases and anomalies in the expression of the UBE3A gene - in most of cases due to defects altering the 15q11-q13 cytogenetic region - can be observed in 90% of the subjects with Angelman phenotype. Nevertheless, there is a percentage of subjects with both disorders, for whom the genetic investigation resulted negative, and this testify the presence of genetic heterogeneity. On the other hand, it has been observed that in an increasing number of subjects, who present with characteristics of both the clinical phenotypes, the diagnostic criteria for either disease are not satisfied. The existence of an AS/RTT-like phenotypic spectrum suggests the existence of a common pathogenetic pathway that involves, at different levels, the protein products of the MECP2 gene and of the UBE3A gene. This hypothesis is supported by the description of cases of Angelman syndrome with mutations of the MECP2 gene. Alterations of the MECP2 gene should therefore be searched for in subjects affected by the classic Rett syndrome or by Angelman syndrome, as well as in AS/RTT like subjects and in all phenotypes that could belong to the "MECP2 related disorder" family. Between 2005 and 2006 it was observed that another gene located on the X chromosome, called CDKL5 or STK9, may be mutated in Rett patients affected by a form of the disease characterised by early onset of seizures.