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BRIEF RESEARCH REPORT article

Front. Pediatr.
Sec. Genetics of Common and Rare Diseases
Volume 12 - 2024 | doi: 10.3389/fped.2024.1450859

In-depth Analysis of OTC A208T Cases Induced by OTC Gene Mutation and Research on the Prediction and Simulation of the Impact on Protein Function

Provisionally accepted
Zhong Li Zhong Li 1*Qingyang Hu Qingyang Hu 1,2Haiming Chen Haiming Chen 3Tianyi Liu Tianyi Liu 1Xue Dong Xue Dong 1,2Xuejiao Hu Xuejiao Hu 1,2Wenxin Yan Wenxin Yan 1,2
  • 1 Department of Pharmacy, Dalian Women and Children’s Medical Group, Dalian, Liaoning Province, China
  • 2 Dalian Medical University, Dalian, Liaoning, China
  • 3 Department of Emergency, Dalian Women and Children’s Medical Group, Dalian, Liaoning Province, China

The final, formatted version of the article will be published soon.

    Ornithine transcarbamylase deficiency (OTCD), a rare hereditary disease caused by gene mutation of ornithine transcarbamylase (OTC), is the most prevalent type among urea cycle disorders. OTCD typically leads to mitochondrial enzyme dysfunction, preventing the synthesis of citrulline from carbamoyl phosphate and ornithine, and is characterized by a remarkable increase in blood ammonia. Specific symptoms may include neurological abnormalities, growth retardation, and other manifestations.We presented a case of a child diagnosed with OTCD (OMIM: 311250). By using whole-genome sequencing (WGS) for the pedigree and in-depth whole-exome sequencing (WES), we aimed to identify the disease-causing genes. Gene mutation prediction tools were employed to verify the pathogenicity, and the molecular dynamics simulation method was utilized to assess the impact of this mutation on the activity and structural stability of the OTC protein.Whole-exome sequencing detected an OTC variant (NM_000531: c.622(exon6) G > A, p.A208T). Through comprehensive analysis with various gene mutation prediction tools and in line with the ACMG guidelines, this mutation site was firmly established as a pathogenic site. Moreover, the molecular dynamics simulation results clearly demonstrated that this mutation would significantly compromise the stability of the OTC protein structure.This study deepens our understanding of the clinical manifestations and characteristics of OTCD, especially the OTC A208T gene mutation site. Given the lack of specific clinical manifestations in OTCD patients, early and accurate diagnosis is crucial for effective treatment and prognosis improvement. To our knowledge, this is the first case of this mutation site reported in China.

    Keywords: Ornithine transcarbamylase deficiency, X-linked disorder, Hyperammonemia, urea cycle disorder, Molecular Dynamics Simulation

    Received: 18 Jun 2024; Accepted: 30 Aug 2024.

    Copyright: © 2024 Li, Hu, Chen, Liu, Dong, Hu and Yan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Zhong Li, Department of Pharmacy, Dalian Women and Children’s Medical Group, Dalian, Liaoning Province, China

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