Ornithine transcarbamylase deficiency (OTCD), an X-linked disorder that results from mutations in the OTC gene, causes\nhyperammonemia and leads to various clinical manifestations. Mutations occurring close to the catalytic site of OTCase can cause\nsevere OTCD phenotypes compared with those caused by mutations occurring on the surface of this protein. In this study, we\nreport two novel OTC missense mutations, Q171H and N199H, found in Malaysian patients. Q171H and N199H caused neonatal\nonset OTCD in a male and late OTCD in a female, respectively. In silico predictions and molecular docking were performed to\nexamine the effect of these novel mutations, and the results were compared with other 30 known OTC mutations. In silico servers\npredicted that Q171H and N199H, as well as 30 known missense mutations, led to the development of OTCD. Docking analysis\nindicated that N-(phosphonoacetyl)-L-ornithine (PALO) was bound to the catalytic site of OTCasemutant structurewith minimal\nconformational changes. However, the mutations disrupted interatomic interactions in the catalytic site. Therefore, depending on\nthe severity of disruption occurring at the catalytic site, the mutation may affect the efficiency of mechanism and functions of\nOTCase.
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