Carbamoyl phosphate synthetase I deficiency: molecular genetic findings and prenatal diagnosis

We report a Japanese boy who died at Day 28 of life because of severe carba moyl phosphate synthetase I (CPS1) deficiency that was proven by enzyme ass ay. By analysis of cDNA and genomic DNA, he was shown to be a compound hete rozygote with two point mutations of the CPS1 gene, 840G > C leading to an aberrant splicing and 1123C > T (predicting Q375X). The 840G > C was a muta tion described in another Japanese family. Since his parents carried each m utation heterozygously, we performed prenatal diagnosis at 16 weeks of his mother's next gestation by multiplex PCR and melting curve analysis in a si ngle capillary containing two-color fluorescent (LC-Red 640 and LC-Red 705) probes oil LightCycler. We analyzed genomic DNA extracted from amniotic ce lls and found that the fetus was homozygous for the wild-type alleles. At t erm a healthy girl was born without hyperammonemia. Copyright (C) 2001 John Wiley & Sons, Ltd.