CARBAMYL-PHOSPHATE SYNTHETASE-I DEFICIENCY - ONE BASE SUBSTITUTION INAN EXON OF THE CPS-I GENE CAUSES A 9-BASEPAIR DELETION DUE TO ABERRANT SPLICING

Carbamyl phosphate synthetase I (CPS I; EC6,3,4,16) is an autosomal re cessive disorder characterized by hyperammonemia. We studied the molec ular bases of CPS I deficiency in a newborn Japanese girl with consang uineous parents. Northern and Western blots revealed a marked decrease in CPS I mRNA and enzyme protein but with a size similar to that of t he control, respectively. Sequencing of the patient's cDNA revealed a nine-nucleotide deletion at position 832-840. Sequencing analysis of t he genomic DNA revealed a G to C transversion at position 840, the las t nucleotide of an exon in the splice donor site. This substitution al tered the consensus sequence of the splice donor site and the newly cr yptical donor site in the exon caused the 9-bp in-frame deletion. This report seems to be the first complete definition of CPS I deficiency, at the molecular level.