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Volume 42 Issue 5
May  2015
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Article Navigation >  Journal of Genetics and Genomics  > 2015  >  42(5): 181-194

Genotype–Phenotype Correlations in Ornithine Transcarbamylase Deficiency: A Mutation Update

doi: 10.1016/j.jgg.2015.04.003
  • a 

    Department of Integrative Systems Biology, Center for Genetic Medicine Research, Children's National Health System, Washington DC 20010, USA

  • b 

    Department of Anthropology, College of Arts and Sciences, Washington University, St. Louis 63130, USA

  • c 

    Graduate School of Biomedical Sciences and Professional Studies, College of Medicine, Drexel University, Philadelphia 19104, USA

More Information
  • Corresponding author: E-mail address: HMorizono@childrensnational.org (Hiroki Morizono)
  • Received Date: 2014-11-26
  • Accepted Date: 2015-04-08
  • Rev Recd Date: 2015-04-05
    • Available Online: 2015-05-19
  • Publish Date: 2015-05-20
    Abstract
  • Ornithine transcarbamylase (OTC) deficiency is an X-linked trait that accounts for nearly half of all inherited disorders of the urea cycle. OTC is one of the enzymes common to both the urea cycle and the bacterial arginine biosynthesis pathway; however, the role of OTC has changed over evolution. For animals with a urea cycle, defects in OTC can trigger hyperammonemic episodes that can lead to brain damage and death. This is the fifth mutation update for human OTC with previous updates reported in 1993, 1995, 2002, and 2006. In the 2006 update, 341 mutations were reported. This current update contains 417 disease-causing mutations, and also is the first report of this series to incorporate information about natural variation of theOTC gene in the general population through examination of publicly available genomic data and examination of phenotype/genotype correlations from patients participating in the Urea Cycle Disorders Consortium Longitudinal Study and the first to evaluate the suitability of systematic computational approaches to predict severity of disease associated with different types of OTC mutations.
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