Gross rearrangements in the MECP2 gene in three patients with Rett syndrome: implications for routine diagnosis of Rett syndrome

Since 1999, many laboratories have confirmed that mutations in the MECP2 gene are the primary cause of Rett syndrome (RTT or RS) and identified mutations in 70 to 90% of the sporadically affected girls. Most of the screenings are PCR-based and restricted to the coding part of the gene and therefore prone to miss gross rearrangements. By Southern blot analysis we identified large deletions (>1 kb) in three female patients with classical, severe Rett syndrome. Further characterization by semi-quantitative PCR and amplification of junction fragments confirmed the presence of a 7.6-kb deletion in one patient and an 8.1-kb deletion in the other patient, both including exon 3 and the coding part of exon 4. The exact nature of the rearrangement in the third patient remained elusive. These results underline the importance of screening for major genomic rearrangements in Rett syndrome. Hum Mutat 22:116-120, 2003.