Causes are due to Lyonization
, post-zygotic somatic mutations during early embryogenesis, gametic half-chromatid mutation occurring before fertilisation.
This phenotypic heterogeneity is due to lyonization
, a process whereby one copy of the X-chromosome is randomly inactivated in all the cells of the female embryo, so that heterozygous females are essentially a "mosaic" of normal and mutant cells in varying proportions.
There is also evidence that, if one X contains abnormal genes, Lyonization
may favour silencing that X over the normal one.
Symptomatic patients are almost exclusively male, but female carriers can be clinically affected due to unfavorable lyonization
1) In females, lyonization
results in functional mosaicism of X-linked genes, which is manifested by the Blaschkoid distribution of cutaneous lesions.
In a normal female cell, there are two copies of the X chromosome; however, only one copy is active, because the other copy is "silenced" through a process called X-inactivation or Lyonization
Females generate both uTP-PCR and mTP-PCR melt peaks, due to Lyonization
of their 2 X chromosomes.
X-inactivation studies, based on the phenomenon of lyonization
Females may present if they are also unfortunate to present with lyonization
8) The pattern of inactivation of the X chromosome in focal nodular hyperplasia, hepatic adenomas, and hepatocellular carcinomas, detected by assaying the DNA methylation patterns of the X-linked human androgen receptor gene (HUMARA), revealed that focal nodular hyperplasia demonstrates a random pattern of lyonization
, consistent with a polyclonal reactive proliferation.
Increased susceptibility of a carrier of X-linked chronic granulomatous disease (CGD) to Aspergillus furnigatus infection associated with age-related skewing of lyonization
The gp91-phox gene is located on the X chromosome, and carriers show a mosaic of nonpathogenic and defective cells, as our patient did, attributable to lyonization