Suspicion of an X-chromosome-linked disorder
As a rule, one of the two X-chromosomes in the cells of females is inactive. Whether the maternal or the paternal X-chromosome is inactive is determined randomly at an early embryonic stage. All subsequent daughter cells carry the identical pattern of activation/inactivation.
Testing for uneven X-inactivation is clinically important for two reasons:
- When an X-chromosomal recessive inherited genetic defect is located on an active X-chromosome but does not hinder the viability of the cell. In this case, X-chromosomal recessive inherited diseases may also be manifest in females.
- When an X-chromosomal dominant inherited genetic defect is located on the inactive X-chromosome. In this case, a woman may show no signs of an X-chromosomal dominant disease but may pass the genetic mutation on to her children.
In addition, some forms of X-chromosomal recessive inherited mental retardation that normally affects only males may be present in females in the form of an uneven distribution of X-inactivation. This serves as an indicator of carrier status.
A genetic defect located on an X-chromosome can be detrimental to the survival of a cell if, in this cell, it is the genetically defect X-chromosome that is active. The advantage or disadvantage of selection can lead to an apparently uneven distribution of X-inactivation favoring the X-chromosome without the genetic defect.
The degree of X-inactivation changes over time; uneven distribution is thus more often found in adult women that in newborn girls. With regard to the extent of the uneven distribution, the following differentiation can be made:
- Non-random X-inactivation: in approximately 99% of cells, the same X-chromosome is active or inactive
- Skewed X-inactivation: in approximately 10% of cells, the same X-chromosome is active or inactive
Analysis of the Androgen Receptor (AR) gene locus located on the X-chromosome. If both alleles can be differentiated at this locus, an analysis of X-inactivation can be performed.
2 - 4 ml of EDTA blood