J Med Genet 37:250-255 doi:10.1136/jmg.37.4.250
  • Original article

Mutation screening in Rett syndrome patients


Rett syndrome (RTT) was first described in 1966. Its biological and genetic foundations were not clear until recently when Amiret al reported that mutations in the MECP2 gene were detected in around 50% of RTT patients. In this study, we have screened theMECP2 gene for mutations in our RTT material, including nine familial cases (19 Rett girls) and 59 sporadic cases. A total of 27 sporadic RTT patients were found to have mutations in the MECP2 gene, but no mutations were identified in our RTT families. In order to address the possibility of further X chromosomal or autosomal genetic factors in RTT, we evaluated six candidate genes for RTT selected on clinical, pathological, and genetic grounds:UBE1 (human ubiquitin activating enzyme E1, located in chromosome Xp11.23),UBE2I (ubiquitin conjugating enzyme E2I, homologous to yeast UBC9, chromosome 16p13.3),GdX (ubiquitin-like protein, chromosome Xq28), SOX3 (SRY related HMG box gene 3, chromosome Xq26-q27),GABRA3 (γ-aminobutyric acid type A receptor α3 subunit, chromosome Xq28), andCDR2 (cerebellar degeneration related autoantigen 2, chromosome 16p12-p13.1). No mutations were detected in the coding regions of these six genes in 10 affected subjects and, therefore, alterations in the amino acid sequences of the encoded proteins can be excluded as having a causative role in RTT. Furthermore, gene expression ofMECP2, GdX, GABRA3, and L1CAM(L1 cell adhesion molecule) was also investigated by in situ hybridisation. No gross differences were observed in neurones of several brain regions between normal controls and Rett patients.


  • * Present address: AstraZeneca R&D Södertälje, 15158 Södertälje, Sweden