How I got LGMD2i
Unbeknownst to my parents they were both carriers of the faulty FKRP gene; they both carried one normal copy and one recessive copy. I had a 1 in 4 chance of getting two recessive copies of the FKRP faulty gene causing me to have LGMD2i.
Children of a parent with LGMD2i
Children of people affected with LGMD2i will have inherited one faulty copy of the Fukutin Related Protein gene and therefore will all be carriers but are unaffected.
If an Affected Parent marries a Carrier (I don't have a picture yet) with each pregnancy their child will have a 50% chance of inheriting one recessive gene making them a carrier and a 50% chance the child will inherit two recessive genes causing them to be affected-to have LGMD2i.
I was confused as to why some Duchenne carriers show symptoms where LGMD2i carriers are unaffected.
Claudia Mitchell from the LGMD2i Research Fund explained:
The reason for the difference between Duchenne and 2i carriers is that the dystrophin gene (the lack of which causes Duchenne) is located in the X chromosome, contrary to the FKRP gene. Women have 2 X copies, while men have one X and one Y chromosome. Since the dystrophin gene is located in the X chromosome, boys only have one copy of this gene and if this one copy is mutated, they will develop the disease. In women, theoretically you would need two mutated copies to develop the disease (as in FKRP). But there is a phenomenon called X inactivation. In every women, during development, one of the X chromosomes gets inactivated.
This can happen as early as at the 2 or 4 cell-stage in the embryo, and the inactivation occurs randomly in each cell. So, sometimes females will have a mosaic pattern of inactivation, with some cells in their body with one X inactive and other cells with the other X inactive. Depending on how many cells inactivated the normal X chromosome during development, Duchenne carriers will have different degrees of disease severity. Since FKRP is located in a chromosome that does not undergo inactivation, you don't see carriers showing symptoms.
If an Affected Parent marries a Carrier (I don't have a picture yet) with each pregnancy their child will have a 50% chance of inheriting one recessive gene making them a carrier and a 50% chance the child will inherit two recessive genes causing them to be affected-to have LGMD2i.
I was confused as to why some Duchenne carriers show symptoms where LGMD2i carriers are unaffected.
Claudia Mitchell from the LGMD2i Research Fund explained:
The reason for the difference between Duchenne and 2i carriers is that the dystrophin gene (the lack of which causes Duchenne) is located in the X chromosome, contrary to the FKRP gene. Women have 2 X copies, while men have one X and one Y chromosome. Since the dystrophin gene is located in the X chromosome, boys only have one copy of this gene and if this one copy is mutated, they will develop the disease. In women, theoretically you would need two mutated copies to develop the disease (as in FKRP). But there is a phenomenon called X inactivation. In every women, during development, one of the X chromosomes gets inactivated.
This can happen as early as at the 2 or 4 cell-stage in the embryo, and the inactivation occurs randomly in each cell. So, sometimes females will have a mosaic pattern of inactivation, with some cells in their body with one X inactive and other cells with the other X inactive. Depending on how many cells inactivated the normal X chromosome during development, Duchenne carriers will have different degrees of disease severity. Since FKRP is located in a chromosome that does not undergo inactivation, you don't see carriers showing symptoms.
If One parent is a carrier
We know our girls are carriers so when they are ready to have children their husband has the option of being tested to see if he is a carrier. Studies show that the carrier risk in the general population is 1 in every 315 people.
If their husband is not a carrier, the picture to the left shows how their children will have a 50% chance of inheriting the recessive gene but will not be affected.
If their husband is not a carrier, the picture to the left shows how their children will have a 50% chance of inheriting the recessive gene but will not be affected.