The relationship between mutation in CPS1 gene and pregnancy loss

Background: Carbamoyl phosphate synthetase 1 (CPS1) is a liver-specific enzyme with the lowest enzymatic rate, which determines the overall rate of the other reactions in the pathway that converts ammonia to carbamoyl phosphate in the first step of the urea cycle. Carbamoyl-phosphate synthetase 1 deficiency (CPS1D) which usually presents as lethal hyperammonemia, is a rare autosomal recessive hereditary disease.Objective: Here we report a case of a two-day-old female neonate with lethal hyperammonemia. The newborn infant presented with hyperammonemia. In Plasma amino acid analysis, there was a significant elevated level of alanine, aspargine, glutamic acid, aspartic acid and lysine. We cannot diagnose the urea cycle disorder (UCD) carbamoyl-phosphate synthetase 1 deficiency (CPS1D) properly only based on the quantity of biochemical intermediary metabolites to exclude other UCDs with similar symptoms.Materials and Methods: We performed Single Nucleotide Polymorphism (SNP) array and after that we performed a whole exome genome sequencing based on next generation sequencing. Sanger sequencing to confirm the mutation was in the patient (homozygous). The mutation was checked in her parent and other family members too.Results: We found a novel missense c. 2758G> C mutation in exon 23 of CPS1 at amino acid position 920 (p. Asp920His). At the end, we used the Sanger sequencing to confirm the mutation was in the patient (homozygous). The mutation was checked in her parent and other family members too.Conclusion: We applied whole exome sequencing (WES) successfully to diagnose the patient with CPS1D in a clinical setting. This result supports the clinical applicability of WES for cost-effective molecular diagnosis of UCDs in prenatal diagnosis to future procedures of disease-free embryo selection.

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words: Carbamoyl-phosphate synthetase 1 deficiency , CPS1 , Urea cycle disorder , Next generation sequencing , Biochemical test