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Mutations in the MECP2 gene in a cohort of girls with Rett syndrome
  1. * Regional Genetics Service, Birmingham Women's Hospital, Birmingham B15 2TG, UK
  2. Medical Genetics Department, St James's University Hospital, Leeds LS9 7TF, UK
  3. University of Birmingham, Section of Medical and Molecular Genetics, Birmingham Women's Hospital, Birmingham B15 2TG, UK
  1. Dr Webb, URL

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Editor—Rett syndrome is a severe, progressive, neurodevelopmental disorder which almost exclusively affects females. At first the affected girls appear to develop normally but after a year to 18 months they begin to deteriorate. Not only do they fail to progress but they lose skills already learnt until finally they have severe developmental delay with dementia and autistic behaviour, an apraxic gait, breathing dysfunction, and stereotyped hand movements, such as excessive hand wringing. Lost skills are not regained.1 The disease, which affects ∼1 in 10 000 girls, accounts for about 10% of profound handicap in females. More than 95% of cases are sporadic leading to the assumption that the syndrome must be the result of an X linked dominant gene with male lethality. Thomas2 has also suggested that the lack of males with the syndrome could be accounted for by the increased rate of de novo germline mutations in males. This would imply that affected females arise as a consequence of de novo mutations in their fathers. Marked skewing of X inactivation has not been detected in sporadic cases of the syndrome either in affected girls or in their mothers,3 but in one familial case the mother of three affected girls was found to have >95% skewing of inactivation in favour of the normal chromosome remaining preferentially active.4 The few available familial cases allowed the gene to be mapped to Xq285 6 and in 1999 Amiret al 7 reported that mutations in the MECP2 gene, located in Xq28, were associated with Rett syndrome in 5/21 of de novo cases. Amiret al 7 and Wanet al 8 reported …

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