Carbamylphosphate synthetase 1 (E.C. 184.108.40.206) deficiency is a rare autosomal recessive disorder of the urea cycle that can result in severe neonatal hyperammonemia. Since the genomic structure of the CPS1 gene was not yet elucidated, mutation detection was performed by analysis of transcripts in the past. Here, we present the entire DNA sequence of the human CPS1 gene including all exon-intron boundaries. Moreover, mutation analysis was performed in six patients leading to the detection of 9 novel mutations including the missense mutations c.2528T>C and c.2623A>G, the nonsense mutations c.712C>T and c.2115ins35bp, the splice site mutations c.1263+5G>C, c.3558+1G>C and c.4101+2T>C, and a small deletion c.3036_3038delGGT. The mutations c.2528T>C and c.2623A>G were identified on a double mutated allele. New data on the genomic structure of the CPS1 gene provided in this study are useful to characterize the heterogenous molecular basis of the disease in patients deficient for carbamylphosphate 1 deficiency.
Copyright 2003 Wiley-Liss, Inc.