Genetics

Today we had an apt with the geneticist to help us decipher the results we got back on my Moms genetics (or at least try to). This may only be interesting for Caroline's relatives...for the rest of you - sorry this may be loooong!

Some facts to start out: Only 5-10% of ALS is passed through genetics and they classify those patients as having "familial" ALS. Of that 5-10% that have familial ALS they can only identify the gene responsible in about 25% of those cases. If they can not find it on a gene that does not mean that it is not familial. Familial ALS does seem to be more aggressive than non-familial ALS. They also usually classify it as "familial" if 2 or more people in a direct line have ALS. My Moms Aunt died of ALS, and it is suspected that my Moms Aunt's cousin also died of ALS. They have assumed because of the family history and the speed of my Moms disease that her ALS is familial, although my Moms Aunt lived for 3 years after symptoms developed so even compared to her Aunt my Mom is going fast.

Now for a quick biology recap: Each human has 23 pairs of chromosomes. They inherit one from each parent making a total of 46 chromosomes all together. On these chromosomes we have "genes" and there are over 30,000. A gene mutation or variation can cause genetic disorders either through a deletion in the sequence or additions. ALS is classified as autosomal dominant which means that only 1 parent has to pass the bad gene, a bad gene will dominate a normal gene. Theoretically this means that if someone has it on their gene - they will get it.

The majority of familial ALS is found on the SOD1 sequence. They are finding new gene mutations that can also cause ALS but these are still very new. In my Moms case there is no sequence alteration on her SOD1, TARDBP, ANG, FIG4 but on her FUS sequence there is a sequence alteration. They have it listed as FUS Variant 1: 3 base pair duplication of CGG. What does that mean? It means there is an amino acid change of unknown clinical significance. And what does that mean??? A genetic mutation of the FUS sequencing has only been linked to ALS in the last year, maybe two. There is simply not enough information to determine if this is what has caused her ALS. She did point out that a 3 base pair duplication is better, or less significant, than a 1 or 2 base pair duplication since it keeps the amino acid chain intact (if you understand what that means feel free to explain it to me)!

The only way to find out if that mutation is significant to her ALS would be to test her Dad and find out if he has this same genetic mutation - because it was his sister that died of ALS. Although if he passed this mutation onto my Mom, and it is a mutation that causes ALS, her dad "theoretically" should have gotten ALS because he would have to have the gene and the gene is suppose to be dominant. Only problem with that is he is 86 and does not have ALS. They explained that all of the genes interact with each other in different ways so someone can have a dominant gene and have it be dormant because of other genetic factors.

What we can conclude: a whole lot of nothing! We don't know if my Mom has familial ALS or not. She does have a genetic sequencing alteration that "could" cause ALS. It can only be proven by finding that genetic mutation in my Grandpa, to prove that the link between his sister and my Mom and also have one of my grandpa or his sisters descendants also get ALS - who also have this same genetic mutation on the FUS sequencing. That would show a direct link between the mutation and ALS. There are Dr's salivating over getting mine, my brothers, my Aunt, and my Moms cousins DNA...at least for me, its not going to happen.

No matter what my brothers and I have a 50/50 chance of having this sequence alteration. My mom has 2 chromosomes to pass so she either passed us her good or the altered. My Moms sister has a 50/50 chance of having that same alteration since one of her parents has to have the mutation. My cousins could have a 50/50 chance of having it - but only if their Mom inherited it like my Mom did. My Moms cousins have a 50/50 chance of having a ALS mutation but only if their Mothers ALS was actually caused by genetics.

It doesn't change anything about the way my Mom is treated, they just are looking for subjects that can help further their understanding of ALS. It is such a unknown disease and we have so little knowledge about what causes it. They are going to do another test on my Mom and look for yet another genetic alteration that they are just discovering the link between that sequencing and ALS.

For now, only time will be able to tell and there is no use worrying about it :)