Reply To: CBS gene mutations being investigated in Ehlers-Danlos.

[tonkadu]

I have two CBS mutations. When I looked the CBS genes up it was noted they are being investigated in…. Ehlers-Danlos!
CBS gene mutations are involved in methylation.

What is “The Methylation Pathway”?????:
http://www.autismnti.com/yourbodyschemistry.html

http://snpedia.com/index.php/Yasko_Methylation
“CBS Gene
rs234706 – CBS C699T (Risk Allele: A) “Being investigated in Ehlers-Danlos syndrome”
rs1801181 – CBS A360A (Risk Allele: T, 23andMe: A) “Being investigated in Ehlers-Danlos syndrome”
rs2298758 – CBS I278T (Risk Allele: G) “Being investigated in Ehlers-Danlos syndrome”

“CBS Gene: Limits homocystine into downstream path. People with CBS mutations will need to be careful with sulfur containing supplements. Increased risk for ammonia detoxification issues. Puts a burden on SUOX.”
http://snpedia.com/index.php/Rs234706
http://snpedia.com/index.php/Rs1801181
http://snpedia.com/index.php/Rs2298758

This is a Gene test for Marfan/TAAD which is listed under the heading “Ehlers-Danlos” and it includes CBS.
http://www.genedx.com/test-catalog/disorders/ehlers-danlos-syndrome/marfan-syndrometaad-sequencing-panel/
Genes on this test: ACTA2, CBS, COL3A1, COL5A1, COL5A2, FBN1, FBN2, MYH11, SLC2A10, SMAD3, TGFBR1, TGFBR2

Read more about CBS mutations:
http://www.heartfixer.com/AMRI-Nutrigenomics.htm

Anyone else have CBS mutations?

Dr. Diana, do you think the sulfur load could be similar to a barrel effect like with histamine? Maybe some patients who haven’t done well on Diamox have CBS mutations and are already over-burdened with sulfur. I wonder if they limited other sulfur sources and got their methylation working better if they might be able to tolerate the Diamox? Hmmmm…. I haven’t tried it yet because I’m so allergic to… sulfa antibiotics but maybe a trial under my allergist’s supervision will be in my future after all. Thoughts?

Hi,
Thank you very much for posting this SweetFeather.

Using 23andme my wife found out she is homozygous positive for the C699T CBS mutation and the A1298C MTHFR mutation.

It’s very interesting to me to see that CBS is being investigated for its role in EDS. I wish there was more of a description re who/what/where is being investigated, but I guess it will be published eventually if any of the investigations are fruitful.

I just want to clarify something I saw. I think there are two different ways that CBS mutations can affect the methylation cycle are being mentioned in your links though.

The link relating to the Marfan Syndrome genetic test I believe is (partly) testing for a mutation in the CBS gene that involves downregulation of CBS and can cause elevated levels of homocysteine and is seen to be responsible for a condition called Homocystinuria that has overlap w/ Marfan (see here, http://www.ncbi.nlm.nih.gov/books/NBK1335/, and here, http://www.ncbi.nlm.nih.gov/books/NBK1524/ – I arrived at these links from the Marfan testing link you posted). I believe those studies refer to the 833T>C and 919G>A mutations of the CBS gene.

The mutations referred to by Dr. Amy Yasko are Y233Y (C699T) and A360A. Yasko says that these mutations involve an upregulation of the CBS gene and that “It’s not surprising that in those with the CBS mutation it’s common to see low levels of homocysteine, cysteine, or cystathionine, due to the rapid conversion to taurine.”

It seems like if these mutations are part of the problem and need addressing, then the directionality of regulation is important.

We’ve only just started on looking into treatment for this, and are planning to read through all of Yasko’s book.