Mutations in the
GCH1,
PCBD1,
PTS and
QDPR genes directly cause BH4 deficiency.
Additionally, mutations of the
MTHFR gene (A1298C variant) and
DHFR can interfere with the recycling of BH4 and lead to less severe, but still clinifically significant, deficiencies of BH4.
anyone test positive for this DHFR snp? p.Asp153Val
http://www.research-in-germany.de/n...enital-genetic-defect,sourcePageId=66910.html
huh. just checked 23andme and I dont' see it. the german researchers describe it as a point mutation.
Aquariusgirl, I see that there wasn't much response here - you might be interested in this thread about DHFR:
http://forums.phoenixrising.me/index.php?threads/snps-for-dihydrofolate-reductase-dhfr.19563/
Regarding the German article you mentioned, the hyperlink appears to no longer work, but I looked it up on yahoo and the rs number seems to be rs104894360:
"ASP153VAL [
dbSNP:rs104894360]"
http://www.omim.org/entry/190070
(23andme doesn't give me anything for that rs number, though)
This is another source mentioning ASP153VAL:
http://www.omim.org/entry/126060
"MEGALOBLASTIC ANEMIA DUE TO DIHYDROFOLATE REDUCTASE DEFICIENCY
DHFR, ASP153VAL
In 3 affected sibs, born of distantly related parents of European descent, with megaloblastic anemia due to dihydrofolate reductase deficiency (
613839),
Cario et al. (2011) identified a homozygous 458A-T transversion in exon 5 of the DHFR gene, resulting in an asp153-to-val (D153V) substitution. Both parents were heterozygous for the D153V mutation, which was not found in 120 control samples. The mutation was predicted to interrupt hydrogen bonding, affecting fold and conformational stability, resulting in decreased enzyme activity. Studies of patient lymphoblastoid cells showed that
DHFR activity was reduced to about 10% of control levels. DHFR expression was similar to controls, but protein levels were severely decreased. Although 1 sib was essentially unaffected except for macrocytosis, the other 2 sibs developed childhood absence epilepsy with eyelid myoclonia in childhood. One had learning disabilities.
Levels of 5-methyltetrahydrofolate (5-MTHF) in the CSF were low, but improved with folinic acid treatment."
The original publication might be this article:
Cario H, Smith DE, Blom H, Blau N, Bode H, Holzmann K, Pannicke U, Hopfner KP, Rump EM, Ayric Z, Kohne E, Debatin KM, Smulders Y, Schwarz K: Dihydrofolate reductase deficiency due to a homozygous DHFR mutation causes megaloblastic anemia and cerebral folate deficiency leading to severe neurologic disease. Am J Hum Genet; 2011 Feb 11;88(2):226-31
http://www.ncbi.nlm.nih.gov/pubmed/21310277
