X chromosome inactivation and X-linked mental retardation
Journal Article
·
· American Journal of Medical Genetics
- Case Western Reserve Univ. School of Medicine, Cleveland, OH (United States)
The expression of X-linked genes in females heterozygous for X-linked defects can be modulated by epigenetic control mechanisms that constitute the X chromosome inactivation pathway. At least four different effects have been found to influence, in females, the phenotypic expression of genes responsible for X-linked mental retardation (XLMR). First, non-random X inactivation, due either to stochastic or genetic factors, can result in tissues in which one cell type (for example, that in which the X chromosome carrying a mutant XLMR gene is active) dominates, instead of the normal mosaic cell population expected as a result of random X inactivation. Second, skewed inactivation of the normal X in individuals carrying a deletion of part of the X chromosome has been documented in a number of mentally retarded females. Third, functional disomy of X-linked genes that are expressed inappropriately due to the absence of X inactivation has been found in mentally retarded females with structurally abnormal X chromosomes that do not contain the X inactivation center. And fourth, dose-dependent overexpression of X-linked genes that normally {open_quotes}escape{close_quotes} X inactivation may account for the mental and developmental delay associated with increasing numbers of otherwise inactive X chromosomes in individuals with X chromosome aneuploidy. 53 refs., 1 fig.
- OSTI ID:
- 476902
- Journal Information:
- American Journal of Medical Genetics, Journal Name: American Journal of Medical Genetics Journal Issue: 1 Vol. 64; ISSN 0148-7299; ISSN AJMGDA
- Country of Publication:
- United States
- Language:
- English
Similar Records
Proposed mechanism of inheritance and expression of the human fragile-X syndrome of mental retardation
Linkage analysis in three families with nonspecific X-linked mental retardation
Lack of X inactivation associated with maternal X isodisomy: Evidence for a counting mechanism prior to X inactivation during human embryogenesis
Journal Article
·
Sat Oct 31 23:00:00 EST 1987
· Genetics; (United States)
·
OSTI ID:5302633
Linkage analysis in three families with nonspecific X-linked mental retardation
Journal Article
·
Fri Jul 12 00:00:00 EDT 1996
· American Journal of Medical Genetics
·
OSTI ID:476924
Lack of X inactivation associated with maternal X isodisomy: Evidence for a counting mechanism prior to X inactivation during human embryogenesis
Journal Article
·
Sun Dec 31 23:00:00 EST 1995
· American Journal of Human Genetics
·
OSTI ID:232384