Abstract
Ornithine transcarbamylase (OTC) deficiency, an X-linked inborn error of the
urea cycle, leads to the accumulation of ammonia, causing neurologic deficits.
Clinical management for the patients with OTC deficiency is frustrating and
requires a burdensome medical regimen, since they may have impairment and
recurrent episodes of hyperammonemia in spite of intensive care. Therefore,
prenatal diagnosis of the affected fetus is important in genetic counselling for
the family at high risk. In this study, mutations in the OTC gene of three
obligate heterozygotes and a proband have been identified in four unrelated
families: R141Q, R320X, H214Y, M205T. Each mutation altered restriction
recognition sites; TaqI for R141Q, NlaIII for M205T, RsaI for H214Y, BclI for
R320X. Based on their molecular defects, prenatal diagnoses of 6 fetuses
including one set of fraternal twins were successfully made at the ninth to
eleventh week of gestation by polymerase chain reaction (PCR)-restriction
digestion using genomic DNA from chorionic villus sampling (CVS). We predicted
the outcome of all fetuses prenatally. Among six, four were females and two were
males, which were determined by PCR amplification of the sex determining region
of the Y chromosome (SRY) gene. Each carried a wild type allele for the
corresponding mutant allele. They were also tested postnatally for the mutations
to be unaffected.