Submicroscopic duplication in Xq28 causes increased expression of the MECP2 gene in a boy with severe mental retardation and features of Rett syndrome.

R ett syndrome is an X linked mental retardation syndrome almost exclusively affecting girls, and has long been regarded as an X linked dominant condition lethal in hemizygous males. Mutations in the gene encoding the methyl-CpG binding protein 2 (MECP2) were demonstrated as the cause of Rett syndrome, and confirmed by a number of studies. The vast majority (95%) of MECP2 mutations occurs de novo. Girls affected by ‘‘classic’’ Rett syndrome show mental retardation and regression, with a typical pattern of symptoms including initially normal development, stagnation, loss of acquired abilities, stereotypic hand movements, regression of speech, profound psychomotor retardation, epilepsy, and autism, although molecular diagnostics has proven that variant clinical forms exist. 4 It has recently been shown that missense mutations in MECP2 can cause severe neonatal encephalopathy in boys. Classic Rett phenotypes in boys have so far only been reported in rare cases of somatic mosaicism or XXY karyotypes. In girls, larger intragenic deletions are responsible for about 11–16% of typical Rett syndrome without point mutations in the coding exons. 13 Larger deletions have not yet been found in boys, and duplications of MECP2 have not yet been reported as a cause for typical Rett syndrome at all. We have established quantitative PCR for diagnosis of deletions affecting MECP2, and in this paper, we report a boy manifesting clinical features of Rett syndrome and a submicroscopic duplication within the cytogenetic band Xq28 encompassing the entire MECP2 gene.