MECP2 mutations in Serbian Rett syndrome patients
Acta Neurol Scand 2007: 116: 413–419.
© 2007 The Authors Journal compilation © 2007 Blackwell Munksgaard. Background –
Rett syndrome is a severe neurodevelopmental X-linked dominant disorder affecting 1/15,000 girls worldwide. Eight years ago, the MECP2 gene was associated with the devastating clinical features observed in Rett syndrome patients. Objectives –
To investigate the spectrum and the frequency of MECP2 mutations in Serbian Rett syndrome patients. Patients and methods –
We screened the MECP2 coding region by conventional mutational screening (single-strand conformation polymorphism/sequencing) in 24 patients of Serbian origin and in their 41 unaffected family members. In search for gene dosage alterations in seemingly mutation-negative girls, we developed a new, specific quantitative PCR method. Results –
Nineteen patients (79%) carried MECP2 mutations, five of which were novel (one nonsense mutation, one duplication and three deletions). Fourteen previously described disease-causing sequence changes and one polymorphism were also detected. Detailed case reports are given for the carriers of the novel mutations. Large MECP2 rearrangements cause Rett syndrome in a significant number of girls without ‘classic’ mutations in this gene. Therefore, we developed a specific quantitative PCR method, covering MECP2 exons 3 and 4, which previously has not been used for screening. No dosage alterations of the two exons were found in the four tested mutation-negative girls. Conclusions –
This is the first genetic study of Rett syndrome in Serbian patients describing the MECP2 mutational and phenotypic spectrum in this population. Detailed clinical descriptions of this ethnically homogeneous patient population add to our knowledge of genotype/phenotype correlations in this severe condition.
Document Type: Research Article
Affiliations: 1: Faculty of Biology, University of Belgrade, Belgrade, Serbia 2: Molecular Biology Unit, School of Biomedical and Health Sciences Beta Cell Group, King’s College London, London, UK 3: Clinic of Neurology and Psychiatry for Children and Youth, School of Medicine, University of Belgrade, Belgrade, Serbia 4: Departments of Neurology 5: Institute of Mother and Child Care of Serbia, Belgrade, Serbia
Publication date: December 1, 2007