A fragile site at 10q23 (FRA10A) in a phenytoin-exposed fetus: a case report and review of the literature.
OBJECTIVE
To report fragility at 10q23.3 in a fetus exposed to phenytoin during pregnancy. Review of the literature.


METHODS
Amniocytes were cultured in A10 (WISENT) culture medium. Molecular polymorphism studies of MTHFR gene using PCR were performed on fetal tissues.


RESULTS
The fragile site was expressed in all 22 amniocyte colonies analyzed. Analysis of fetal blood showed 46,XX[98]/46,XX,fra(10)(q23.3)[3]/46,XX,del(10)(q23.3) [1]. Molecular studies of the MTHFR (methylenetetrahydrofolate reductase) gene identified a compound heterozygote genotype for two polymorphisms, 677C>T and 1298A>C.


CONCLUSIONS
The fragility at 10q23.3 is unlikely to be due to culture condition-induced folic acid deficiency (medium contains folate). It is possible that this finding represents a previously undescribed folic acid-insensitive fragile site in the region of 10q23.3. Alternatively, the fetal cells may have had decreased folate metabolism, and the fragile site was the known folate-sensitive FRA10A. Since phenytoin has been shown to decrease MTHFR activity in mice, we postulate that the fragile site at 10q23.3 in this fetus may have arisen secondary to a combination of the polymorphisms in MTHFR and exposure to this drug, and is indeed FRA10A.
Morel
Chantal F
CF
F. Clarke Fraser Clinical Genetics Unit, Division of Medical Genetics, Department of Pediatrics, Montreal Children's Hospital, Montreal, Québec H3H 1P3, Canada. chantal.morel@mail.mcgill.ca
Duncan
Alessandra M V
AM
Désilets
Valérie
V
D000328:Adult; D000649:Amniocentesis; D000927:Anticonvulsants / Q000627:therapeutic use*; D002478:Cells, Cultured; D002872:Chromosome Deletion; D043283:Chromosome Fragile Sites / Q000187:drug effects / Q000235:genetics*; D002873:Chromosome Fragility / Q000187:drug effects / Q000235:genetics*; D002879:Chromosomes, Human, Pair 10; D004827:Epilepsy / Q000188:drug therapy; D005260:Female; D006801:Humans; D007621:Karyotyping; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D010672:Phenytoin / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy
D000927:Anticonvulsants; D010672:Phenytoin; D042965:Methylenetetrahydrofolate Reductase (NADPH2)