MTHFR mutation. A genetic riddle I can't solve. Urgent!

Post Reply New Topic

Hello.

I'm talking about C677T mutation. Which is related to folate metabolism. This mutation is autosomal recessive.
MTHFR mutation has been associated with Schizophrenia, autism, and some other stuff.

someones mother has confirmed homozygote MTHFR C677T mutation. I suppose it means both genes are bad..
her daughter has confirmed heterocygotzygote MTHFR C677T mutation. I suppose it means one broken gene.

1. What are the chances that her son has homozygote MTHFR mutation???
2. What are the chances that her son has heterozygote MTHFR mutation???
3. Can one find out (based on this information) whether the father of these also has the mutation???

I need to know this. badly. Please explain this to me.
Thanks for your fast replies.

Lets assume that the gene is not sex linked (not on the X Y chromosomes).

Lets say that most folks have two copies of the good A version of the gene. So most folks are AA.

You know that the mom has two bad (B) versions of the gene. So mom is BB.

The daughter AB.

So what is the dad?

We dont know. The daughter got an A from him. So he could be either AA (most likely because thats whats most common). Or he could be AB like the daughter (unlikely, but not impossible).

If the Dad is AA then all offspring would be hetero AB.

But if Dad is AB then half of the children would be AB (heterozygote), and half would be BB (homozygote for the bad version).

They taught us in the seventh grade to set it up with a table this way ( for two heterozygote parents in this case):

A.....B
A aa ab

B ab bb


The horizontal is one parent, the vertical the other. The lowercase in the middle where they cross are the possible combinations for the offspring.

For two heterozygote parents it comes out to one quarter AA, one half AB, and one quarter BB.

Ok thanks. I thought it would be so too. But wanted smart people to take a look at it. heterozygote C677T mutation on it's own causes massive problem. Even when it's "just" heterozygote.

Homozygous = both copies of the gene have the same allele.
Heterozygous = the two copies of the gene have different alleles. (in this case presumably one standard and one C677T mutation.)

An autosomal recessive allele only has an impact if it's homozygous.



Whose son? The mother's, or the daughter's?

In each case, it depends on the father's genotype. Here are the possible combinations for both the mother's offspring and the daughter's offspring, depending on the father's genotype.

Based on the daughter's genotype, her father must have at least one standard allele. So he could either have standard/standard or standard/C677T genotype.

If he has standard/standard and the mother has C677T/C677T, the only possible result is standard/C677T. So the son would be a heterozygote like his sister.

If he has standard/C677T, then there's a 50% chance of standard/C677T and a 50% chance of C677T/C677T genotype. So their son could have either genotype. (Note: each child is independent. The fact that their daughter is standard/C677T doesn't mean the son would be the other option to balance out.)

For the daughter's own children, she could end up with a guy of any of the three possible genotypes (standard/standard, standard/C677T or C677T/C677T).

If she had a child with a C677T/C677T guy, the results would be the same as described above.

If the guy had standard/standard, then they'd have 50% chance of a child with a standard/standard genotype and a 50% chance of a standard/C677T genotype.

If the guy had standard/C677T, then their child has a 25% chance of having the C677T/C677T genotype, a 50% chance of the standard/C677T genotype and a 25% chance of the standard/standard genotype.

I watched a YouTube video today (I think it was this one: https://www.youtube.com/watch?v=wbXxQkPY0Ik) that said this gene is mutated in 98% of people with autism. I've just ordered a 23andMe gene test and if it doesn't give information about this gene, I can upload results to GeneticGenie to find out if I have one of those variants.

I have a heterozygous mutation so I have diminished methylation, about 40% compared to homozygous which is around 70% however my first child was born with a cleft palate due to folate deficiency. The obstetrician told me I had to have supplemental folate if I was planning on having more kids. Back them I had no idea I had a MTHFR defect and while it's not possible to prove the two are related, it is suggestive. Since I've learnt that I have it, I take SAM-e which is a methyl donor, folate and B6 and B12. It helps.

I downloaded the raw data yesterday and I have a homozygous C677T mutation. Interesting, this article suggests a strong correlation between the implementation of folic acid fortification and a dramatic increase in prevalence of autism: http://mthfr.net/folic-acid-fortification-increase-in-mthfr-and-rise-in-autism/2012/05/11/ I've started taking methylfolate and methylcobalamin, but this is still very new to me... I'll post a follow-up if I find more information worth sharing.

I have MTHFR and use methylfolate and methylcobalamin as well as pyridoxal-5-phosphate (active form of vitamin B6). These make a huge difference. I also have a deficiency of intrinsic factor that impairs absorption of B12. Genetic methylation defects are not uncommon with autism. I used to take dimethyl and trimethyl glycine (betaine) as methyl donors. Thanks for the information about SAM-e, I need to resume taking this as well.