What is Lowe syndrome?

In order to prevent females from expressing double the amount of the genes on the X chromosome compared to males who have one X and one Y, one X in females is randomly inactivated early in development. Because the process is random, a female will have, on average, about half of her cells with one X active and other half of her cells with the other X active. In some very rare cases the process may be disrupted so that a female has only one of her X chromosomes active in most or all of her cells. If this occurs and she is a carrier for an X-linked recessive disorder, like Lowe syndrome, and the X chromosome with the mutation is the active one, she will express only the gene with the mutation and will not express a normal gene to compensate, and she could have Lowe syndrome.

Balanced X chromosome:autosome translocation involves the concept of X-inactivation. A chromosomal translocation is a chromosome defect that occurs due to an error of chromosome segregation. If it occurs during the formation of the egg or sperm all the cells in the offspring will have the abnormality. Essentially what happens in a translocation event is that one chromosome can break and “stick” to a different chromosome. In the case of a balanced translocation a piece of one chromosome gets broken and stuck to another broken chromosome, and vice versa, so that the chromosomes actually switch ends. It is called balanced, because all the genetic material is still there (so you could get a piece of one of your chromosome 1’s stuck onto one of your chromosome 2’s and vice versa). People can be balanced translocation carriers are often normal themselves, depending on where the break occurs. Remember that even if the break disrupts a gene, they also have the possibility of having a normal copy on their full-length non-translocated chromosome, to compensate for the gene disrupted by the break. However, if there is a balanced translocation that occurs in the egg, involving the X and an autosome (non-sex chromosome) this creates a problem, since normally one of the X’s in females becomes inactive.

The process of inactivation, travels all down the chromosome, so that if the X with the balanced translocation was inactive, you would not only lose the X chromosome genes, but also the genes from the autosome that is translocated onto the X,–big problem– the fetus would likely not survive with a large loss of all the genes from the translocated autosome. What happens in the case of an X:autosome translocation is that another mechanism kicks in to compensate for this. The X with the translocation will be the one that stays active (overriding the “random X-inactivation” process). The result of the X with the translocation being active is that there may be genes that are disrupted at the breakpoint, the place where the two chromosomes are joined, and there is not another active X chromosome with a normal gene to compensate. If the break were to occur in the Lowe syndrome gene, that female would have only one active X, the translocated one, which has the mutation in the Lowe syndrome gene. Therefore she would have Lowe syndrome, since she would have one copy of the mutated gene in all of her cells, just like a boy with Lowe syndrome. This is an extremely rare event, since the break would have to occur within the OCRL1 gene.