{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:54:21Z","timestamp":1776128061165,"version":"3.50.1"},"reference-count":41,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,4,26]],"date-time":"2017-04-26T00:00:00Z","timestamp":1493164800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Laboratory Analysis"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Carbamoyl Phosphate Synthetase 1 deficiency (<jats:styled-content style=\"fixed-case\">CPS<\/jats:styled-content>1D) is a rare autosomal recessive inborn metabolic disease characterized mainly by hyperammonemia. The fatal nature of <jats:styled-content style=\"fixed-case\">CPS<\/jats:styled-content>1D and its similar symptoms with other urea cycle disorders (<jats:styled-content style=\"fixed-case\">UCD<\/jats:styled-content>s) make its diagnosis difficult, and the molecular diagnosis is hindered due to the large size of the causative gene <jats:italic><jats:styled-content style=\"fixed-case\">CPS<\/jats:styled-content>1<\/jats:italic>. Therefore, the objective of the present study was to investigate the clinical applicability of exome sequencing in molecular diagnosis of <jats:styled-content style=\"fixed-case\">CPS<\/jats:styled-content>1D in Chinese population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We described two Chinese neonates presented with unconsciousness and drowsiness due to deepening encephalopathy with hyperammonemia. Whole exome sequencing was performed. Candidate mutations were validated by Sanger sequencing. In\u2010silicon analysis was processed for the pathogenicity predictions of the identified mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Two compound heterozygous mutations in the gene carbamoyl phosphate synthetase 1(<jats:italic><jats:styled-content style=\"fixed-case\">CPS<\/jats:styled-content>1)<\/jats:italic> were identified. One is in Case 1 with two novel missense mutations (c.2537C&gt;T, p. Pro846Leu and c.3443T&gt;A, p.Met1148Lys), and the other one is in Case 2 with a novel missense mutation (c.1799G&gt;A, p.Cys600Tyr) and a previously reported 12\u2010bp deletion (c.4088_4099del, p.Leu 1363_Ile1366del). Bioinformatics deleterious predictions indicated pathogenicity of the missense mutations. Conversation analysis and homology modeling showed that the substituted amino acids were highly evolutionary conserved and necessary for enzyme stability or function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The present study initially and successfully applied whole exome sequencing to the molecular diagnosis of <jats:styled-content style=\"fixed-case\">CPS<\/jats:styled-content>1D in Chinese neonates, indicating its applicability in cost\u2010effective molecular diagnosis of <jats:styled-content style=\"fixed-case\">CPS<\/jats:styled-content>1D. Three novel pathogenic missense mutations were identified, expanded the mutational spectrum of the <jats:italic><jats:styled-content style=\"fixed-case\">CPS<\/jats:styled-content>1<\/jats:italic> gene.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcla.22241","type":"journal-article","created":{"date-parts":[[2017,4,26]],"date-time":"2017-04-26T09:57:18Z","timestamp":1493200638000},"source":"Crossref","is-referenced-by-count":15,"title":["Carbamoyl phosphate synthetase 1 deficiency diagnosed by whole exome sequencing"],"prefix":"10.1002","volume":"32","author":[{"given":"Guoqing","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Neonatology Shanghai Children's Medical Center Shanghai Jiaotong University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yulin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Shanghai Children's Medical Center Shanghai Jiaotong University 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