11/03/2013
X-Linked
X-linked Alport syndrome is the most common form, accounting for at least 80 percent of people with the disease. X-linked Alport syndrome results from mutations in the gene that produces the alpha-5 chain of type IV collagen, which is located on the X chromosome. Males have only one X chromosome, so boys with mutations in the alpha-5 chain are severely affected and always develop kidney failure sometime in their lives, because they do not have a normal copy of the gene to buffer the effect of the mutant gene. Girls, who have two X chromosomes, have two copies of the alpha-5 chain gene. In girls with X-linked Alport syndrome, one copy of the alpha-5 chain gene carries a mutation, but the other copy is normal. The normal copy of the gene counters the effect of the mutation, so that girls with X-linked Alport syndrome usually have milder symptoms than boys. However, girls with X-linked Alport syndrome may also develop kidney failure.
Because men pass their X chromosomes to their daughters but not to their sons, a man with X-linked Alport syndrome will pass the disease to all of his daughters but his sons cannot inherit the disease. As for a woman with X-linked Alport syndrome, every time she is pregnant there is a 50:50 chance she will pass the X chromosome carrying the mutant alpha-5 chain gene (and the disease) to the baby, whether the baby is a girl or a boy.
How is X-linked AS inherited?
Alport syndrome is much more common in boys and men because the gene that usually causes it (called COL4A5) is on the X chromosome. Women have two X chromosomes (XX), so they usually have a normal copy as well as an abnormal copy of the gene. Men have only one X chromosome (XY), so if they have a problem with the COL4A5 gene, that is their only copy. Boys who inherit the disease in this way must inherit it from their mother (as the mother contributes the X chromosome and the father the Y).
GENETICS LINK DATA:
Q. Females usually don't end up with kidney failure. How could this be?
A: Alport syndrome is caused by a mutated X chromosome. Females have two Xs and males have one X, one Y. Because of that, females have a "backup" of sorts: the healthy parent's X chromosome protects the female from much of the effects of the bad X. Males only have the one X, so their bodies have no healthy X to protect them. In Alport sufferers, it looks something like this.
Q: Does Alport Syndrome pass from the male to his children?
A: Again, it goes back to the chromosomes: females have two Xs, males have an X and a Y. Therefore, a male will always pass along his X to his daughter(s) and his Y to his son(s). Because of this, the daughter of a male Alport Syndrome sufferer will always inherit his diseased X chromosome, and the son of such a man will never inherit the disease from him (because the son gets the Y from dad--which isn't affected by the disease--and he receives his X chromosome from his mom):
Women who carry the disease on one of their X chromosomes may have minor kidney trouble, such as blood or protein in the urine, sometimes with high blood pressure, but occasionally get severe disease and develop kidney failure. The lifetime risk of severe kidney disease for women who carry Alport's may be as high as 1 in 5, but most never get severe trouble, and those who do are usually much older than men who are affected.
In other families the gene involved (COL4A3 and COL4A4) is on another chromosome. In this case, men and women are equally affected, but otherwise the disease seems the same.
