In Silico Analysis of a De Novo OTC Variant as a Cause of Ornithine Transcarbamylase Deficiency

• Published in: Applied immunohistochemistry & molecular morphology Vol. 30; no. 2; pp. 153 - 156
• Main Authors: Ozdemir, Yesim, Cag, Murat, Gul, Seref, Yüksel, Zafer, Ergoren, Mahmut C.
• Format: Journal Article
• Language: English
• Published: United States Lippincott Williams & Wilkins 01-02-2022
• Subjects: Humans; Hyperammonemia - complications; Ornithine Carbamoyltransferase Deficiency Disease - complications; Ornithine Carbamoyltransferase Deficiency Disease - genetics; Whole Exome Sequencing
• ISSN: 1541-2016; 1533-4058
• DOI: 10.1097/PAI.0000000000000979

Ornithine transcarbamylase deficiency (OTCD) is the most common X-linked hereditary disorder of urea cycle disorders that is caused by neonatal hyperammonemia. OTC gene sequence variations are common causes of OTCD. The current study presents a 28-month-old baby girl proband with phenotypical characteristics of OTCD such as irritability, somnolence, intermittent vomiting, and high levels of serum ammonium. Whole-exome sequencing revealed a de novo c.275G>A p.(Arg92Gln) variant within the OTC gene. In silico analysis revealed a possible differential affinity between wild-type and mutant OTCase, while Arg92Gln decreases the binding ability of OTCase to the substrate, which can disrupt the urea cycle and explains the molecular pathogenicity of clinical hyperammonemia. In light of the fact that the genotype and phenotype correlation of OTCD is still uncertain, the present in silico analysis outcome can enhance our knowledge on this complicated, rare, and severe genetic disorder.