title: Fetal anticonvulsant syndromes and polymorphisms in MTHFR, MTR, and MTRR.
abstract: The malformations found in fetal anticonvulsant syndromes (FACS) are associated with folic acid deficiency and methylene-tetrahydrofolate reductase (MTHFR) polymorphisms in the general population. To investigate a possible association between FACS and MTHFR genotype, we recruited 200 mothers who had taken anti-epileptic drugs in pregnancy, and delivered at Aberdeen Maternity Hospital over a 26-year period. Clinical findings in the mothers and their 337 children were documented. A clinical algorithm was devised to diagnose FACS objectively. Case-parent triads were genotyped for polymorphisms in MTHFR, serine hydroxymethyl transferase (SHMT1), methionine synthase (MTR), and methionine synthase reductase (MTRR), and analyzed by log-linear regression. No effect of the child's genotype on congenital malformation, neurodevelopmental disorder or FACS was detected using this method. The risk of having a child with congenital malformation or FACS was three to four times higher for mothers who were MTHFR 677TT homozygotes compared with MTHFR 677CC homozygotes. MTR 2756A > G and MTRR 66A > G genotype frequencies in children with FACS and neurodevelopmental disorder were different from those in healthy blood donor controls.
authors.affiliation: Department of Medical Genetics, Clinical Genetics Centre, University of Aberdeen, Aberdeen, Scotland, United Kingdom. j.dean@abdn.ac.uk
authors.forename: John
authors.initials: J
authors.lastname: Dean
authors.forename: Zoe
authors.initials: Z
authors.lastname: Robertson
authors.forename: V
authors.initials: V
authors.lastname: Reid
authors.forename: Q Diana
authors.initials: QD
authors.lastname: Wang
authors.forename: Hazel
authors.initials: H
authors.lastname: Hailey
authors.forename: Sue
authors.initials: S
authors.lastname: Moore
authors.forename: A Dee
authors.initials: AD
authors.lastname: Rasalam
authors.forename: Peter
authors.initials: P
authors.lastname: Turnpenny
authors.forename: David
authors.initials: D
authors.lastname: Lloyd
authors.forename: Amanda
authors.initials: A
authors.lastname: Cardy
authors.forename: Duncan
authors.initials: D
authors.lastname: Shaw
authors.forename: Julian
authors.initials: J
authors.lastname: Little
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics*; D000927:Anticonvulsants; D005287:Ferredoxin-NADP Reductase / Q000235:genetics*; D005787:Gene Frequency; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D013577:Syndrome
chemical_list: D000927:Anticonvulsants; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase