Abstract
Rett syndrome (RTT), an X-linked dominant neurodevelopmental disorder in females, is caused mainly by de novo mutations in the methyl-CpG-binding protein 2 gene (MECP2). Here we report mutation analysis of the MECP2 gene in 87 patients with RTT from the Czech and Slovak Republics, and Ukraine. The patients, all girls, with classical RTT were investigated for mutations using bi-directional DNA sequencing and conformation sensitive gel electrophoresis analysis of the coding sequence and exon/intron boundaries of the MECP2 gene. Restriction fragment length polymorphism analysis was performed to confirm the mutations that cause the creation or abolition of the restriction site. Mutation-negative cases were subsequently examined by multiple ligation-dependent probe amplification (MLPA) to identify large deletions. Mutation screening revealed 31 different mutations in 68 patients and 12 non-pathogenic polymorphisms. Six mutations have not been previously published: two point mutations (323T>A, 904C>T), three deletions (189_190delGA, 816_832del17, 1069delAGC) and one deletion/inversion (1063_1236del174;1189_1231inv43). MLPA analysis revealed large deletions in two patients. The detection rate was 78.16%. Our results confirm the high frequency of MECP2 mutations in females with RTT and provide data concerning the mutation heterogeneity in the Slavic population.
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Acknowledgments
We are grateful to the patients and their families for participating in this study. We would like to thank the physicians who referred their patients with RTT to us and provided us with blood samples, workers from the Institutes of social work for mentally retarded children from Vyskov and Ceske Budejovice, and A. Puchmajerova for technical assistance. This work was supported by grants from the Ministry of Health IGA MZ 8355-3 (D.Z, P.M., and J.Z.) and the Grant Agency of the Charles University GAUK 8/04 (D.Z. and P.M).
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MLPA probes in and around the MECP2 gene included in the SALSA MLPA P015C MECP2 Kit (according to the MRC Holland product sheet, http://www.mrc-holland.com/pages/p015pag.html) (DOC 37.5 KB)
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Zahorakova, D., Rosipal, R., Hadac, J. et al. Mutation analysis of the MECP2 gene in patients of Slavic origin with Rett syndrome: novel mutations and polymorphisms. J Hum Genet 52, 342–348 (2007). https://doi.org/10.1007/s10038-007-0121-x
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DOI: https://doi.org/10.1007/s10038-007-0121-x
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