Mutated methylenetetrahydrofolate reductase as a risk factor for spina bifida.
Periconceptional folate supplementation reduces the risk of neural-tube defects. We studied the frequency of the 677C-->T mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene in 55 patients with spina bifida and parents of such patients (70 mothers, 60 fathers). 5% of 207 controls were homozygous for the 677C-->T mutation compared with 16% of mothers, 10% of fathers, and 13% of patients. The mutation was associated with decreased MTHFR activity, low plasma folate, and high plasma homocysteine and red-cell folate concentrations. The 677C-->T mutation should be regarded as a genetic risk factor for spina bifida.
van der Put
N M
NM
Department of Pediatrics, University Hospital Nijmegen, Netherlands.
Steegers-Theunissen
R P
RP
Frosst
P
P
Trijbels
F J
FJ
Eskes
T K
TK
van den Heuvel
L P
LP
Mariman
E C
EC
den Heyer
M
M
Rozen
R
R
Blom
H J
HJ
D000328:Adult; D005260:Female; D005492:Folic Acid / Q000097:blood; D005787:Gene Frequency; D006710:Homocysteine / Q000097:blood; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D017354:Point Mutation; D012307:Risk Factors; D016135:Spinal Dysraphism / Q000235:genetics*
D006710:Homocysteine; D005492:Folic Acid; D000587:Oxidoreductases Acting on CH-NH Group Donors