Balanced X chromosome inactivation patterns in the Rett syndrome brain
| Autor: | Mona D. Shahbazian, Huda Y. Zoghbi, Yaling Sun |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Adult
congenital hereditary and neonatal diseases and abnormalities Adolescent Genotype Genetic Linkage DNA Mutational Analysis Rett syndrome Biology X-inactivation Genetic determinism Frameshift mutation MECP2 Dosage Compensation Genetic medicine Rett Syndrome Humans Amino Acids Child Genetics (clinical) X chromosome Genetics Chromosomes Human X Chromosome Brain DNA medicine.disease CpG site Mutation Female |
| Zdroj: | American journal of medical genetics. 111(2) |
| ISSN: | 0148-7299 |
| Popis: | In Rett syndrome (RTT), an X-linked disorder essentially limited to females, neurological development goes awry. Causing this disarray in neuronal function is a mutated form of a protein known as methyl-CpG-binding protein 2 (MeCP2). Because the MECP2 gene is subject to X chromosome inactivation (XCI) in females, a number of studies have addressed whether the percentage of cells inactivating the normal vs. mutant chromosome in heterozygous females influences the phenotypic outcome of MECP2 mutations. Because most of these studies measured XCI in peripheral blood, however, interpretation of the results requires the assumption that XCI patterns in blood are representative of those in the brain, the primarily affected tissue. Here, we have analyzed the MECP2 sequence and XCI status in 13 brains of RTT patients. Mutations were identified in nine of the cases, with eight of these representing C to T transitions at CpG dinucleotides, and one being a novel frameshift mutation (765delA). Patterns of XCI were balanced in 10 of 10 cases for which the assay was informative. As previous studies have shown that a majority of RTT patients have balanced XCI patterns in peripheral blood, our results suggest that the pattern in blood is an accurate indicator of XCI patterns in the brain for a majority of cases, but there are some notable exceptions that this study may help explain. Given the correlation between balanced XCI and classic RTT, these results suggest that a certain percentage of neurons expressing the mutant MECP2 gene may be required for RTT to become manifest. © 2002 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text