Preimplantation testing for phenylketonuria.
OBJECTIVE
To use preimplantation genetic diagnosis to achieve a phenylketonuria-free pregnancy in a couple at 50% risk for producing an affected child.


METHODS
DNA analysis of the first and second polar bodies (PB1 and PB2) obtained from oocytes of a heterozygous mother in IVF-ET, with the goal of identifying and transferring back to the patient the embryos resulting from mutation-free oocytes.


METHODS
IVF program of Reproductive Genetics Institute, Chicago, Illinois.


METHODS
A mother carrying the R408W mutation and a father with compound heterozygosity for R408 and Y414C mutations in phenylalanine hydroxylase (PAH) gene.


METHODS
Removal and testing for maternal mutation in PB1 and PB2 from each oocyte after standard IVF.


METHODS
DNA analysis of PB1 and PB2 indicating whether corresponding oocytes were mutation-free, for the purposes of transferring only unaffected embryos resulting from these oocytes.


RESULTS
Of 11 zygotes with both PB1 and PB2, 6 were predicted to be free of phenylketonuria. Of these, 4 were transferred, resulting in an unaffected twin pregnancy and birth of two healthy children.


CONCLUSIONS
Preimplantation genetic diagnosis of phenylketonuria resulted in the birth of phenylketonuria-free children. Preimplantation genetic diagnosis by PB analysis in couples with a compound heterozygous male partner is clinically useful.
Verlinsky
Y
Y
Reproductive Genetics Institute, Chicago, Illinois, USA. rgi@flash.net
Rechitsky
S
S
Verlinsky
O
O
Strom
C
C
Kuliev
A
A
D000328:Adult; D004624:Embryo Transfer; D047108:Embryonic Development; D005260:Female; D005307:Fertilization in Vitro; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D009154:Mutation; D010651:Phenylalanine Hydroxylase / Q000235:genetics; D010661:Phenylketonurias / Q000175:diagnosis*; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D015183:Restriction Mapping
D010651:Phenylalanine Hydroxylase