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Spontaneous recurrent mutations and a complex rearrangement in the MECP2 gene in the light of current models of mutagenesis.
- Source :
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Mutation research [Mutat Res] 2012 Jun 01; Vol. 734 (1-2), pp. 69-72. Date of Electronic Publication: 2012 Apr 16. - Publication Year :
- 2012
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Abstract
- Mutations in the methyl-CpG-binding protein 2 (MECP2) gene are associated with Rett syndrome (RTT). The MECP2 gene has some unique characteristics: (1) it is mainly affected by de novo mutations, due to recurrent independent mutational events in a defined "hot spot" regions or positions; (2) complex mutational events along a single allele are frequently found in this gene; (3) most mutations arise on paternal X chromosome. The recurrent point mutations involve mainly CpG dinucleotides, where C>T transitions are explained by methylation-mediated deamination. The complex mutational events might be explained by the genomic architecture of the region involving the MECP2 gene. The finding that most spontaneous mutations arise on paternal X-chromosome supports the higher contribution of replication-mediated mechanism of mutagenesis. We present 9 types of mutations in the MECP2 gene, detected in a group of 22 Bulgarian and 6 Romanian classical RTT patients. Thirteen patients were clarified on molecular level (46.4%). The point mutations in our sample account for 61.5%. One intraexonic deletion was detected in the present study (7.7%). One novel insertion c.321&#95;322insGAAG, p.(Lys107&#95;Leu108insGluAlafs2*) was found (7.7%). Large deletions and complex mutations account for 23%. A novel complex mutational event c.[584&#95;624del41insTT; 638delTinsCA] was detected in a Romanian patient. We discuss different types of the MECP2 mutations detected in our sample in the light of the possible mechanisms of mutagenesis. Complex gene rearrangements involving a combination of deletions and insertions have always been most difficult to detect, to specify precisely and hence to explain in terms of their underlying mutational mechanisms.<br /> (Copyright © 2012 Elsevier B.V. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 0027-5107
- Volume :
- 734
- Issue :
- 1-2
- Database :
- MEDLINE
- Journal :
- Mutation research
- Publication Type :
- Academic Journal
- Accession number :
- 22525432
- Full Text :
- https://doi.org/10.1016/j.mrfmmm.2012.04.001