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Gene: CPS1

Green List (high evidence)

Metabolic disorder with two main forms: a lethal neonatal type and a less severe, delayed-onset type (onset ages reported range from late first, into third decade). Carbamoyl phosphate synthetase I deficiency is an autosomal recessive inborn error of metabolism of the urea cycle which causes hyperammonemia.

PMID:8486760
Identified a homozygous missense mutation in a newborn Japanese girl with CPS I deficiency.

PMID:17310273
Identified 25 different mutations in the CPS1 gene, including 19 novel mutations n 16 of 18 in Japanese patients with a clinical diagnosis of CPS I deficiency. Two patients with confirmed CPS I deficiency had later onset at ages 13 and 31 years, respectively. Genotype/phenotype correlations were not observed.

PMID:21120950
By analyzing tissue and DNA samples from 205 individuals with CPS I deficiency spanning 24 years, Haberle et al. (2011) identified 192 different pathogenic mutations in the CPS1 gene, including 130 novel mutations. When combined with previously reported mutations, it was clear that most mutations (90%) were private, occurring in only 1 family each. The few recurrent mutations tended to occur at CpG dinucleotides. Most missense mutations occurred around exon 24, at the boundary between both homologous halves of the region encoding the 120-kD catalytic moiety of the enzyme. Mutations also clustered at the bicarbonate and carbamate phosphorylation domains, at the NAG cofactor binding domain, and at the interface between the large and small subunit-like moieties. Comparative modelling using the E. coli enzyme showed that the location of missense mutations correlated with evolutionary importance and included internal residues, suggesting that they affect protein folding.

Created: 17 Oct 2024, 11:21 a.m. | Last Modified: 17 Oct 2024, 11:21 a.m.

Panel Version: 1.420

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Carbamoylphosphate synthetase I deficiency MIM#237300

Publications

• 8486760 17310273 21120950 9862865 29801986 27834067 27150549 22173106