Etiopatogeneza i zasady diagnostyki molekularnej zespołu Retta

Rett syndrome (RTT) is a progressive neurodevelopmental disorder with X-linked dominant inheritance. Clinical features are observed almost exclusively in females. Rett syndrome is one of the most common causes of mental retardation in females. RTT is characterized by the apparently normal development for the first months of life followed by the neurodevelopmental arrest and even the regression of acquired skills. Except classical RTT there exist RTT variants with the wide variability in severity of clinical symptoms. Mutations in MECP2 gene, coding for a transcription repressor MeCP2, are identified in RTT patients. The MeCP2 protein acts specifically in the central nervous system, regulating the expression of genes coding proteins necessary for the proper function of the system. Up to now, 490 various mutations in MECP2 gene have been revealed; almost all are de novo. Pathogenic mutations in MECP2 gene are identified in around 80-90% of patients with classical RTT and in 20-40% of patients with RTT variants. Mutations in other genes: CDKL5, NTNG1 and FOXG1, can be found in some patients with atypical forms of RTT. The analysis of four MECP2 gene exons, that allows to identify small mutations, is the basis of the Rett syndrome molecular diagnostics. Moreover, technics enabling the identification of large rearragements in MECP2 gene and the adjacent Xq28 region, are used. Molecular investigations of MECP2 gene have been conducted in the Department of Medical Genetics IP-CZD in Warsaw since 2002 and resulted in identification of mutations in 77 females and one male. The molecular analysis of MECP2 gene allows to confirm the Rett syndrome clinical recognition in many cases; however, the high rate of the mutation detection in that gene can be expected only in patients with classical RTT.