Analysis of mRNA transcripts improves the success rate of molecular genetic testing in OTC deficiency.

Abstract

BACKGROUND:

Ornithine transcarbamylase (OTC) deficiency is the most common inborn error of urea metabolism that can lead to hyperammonemic crises and orotic aciduria. To date, a total of 341 causative mutations within the OTC gene have been described. However, in about 20% of the patients with enzymatically confirmed OTC deficiency no mutation can be detected when sequencing of genomic DNA analyzing exons and adjacent intronic segments of the OTC gene is performed.

METHODS:

Standard genomic DNA analysis of the OTC gene in five consecutive patients from five families revealed no mutation. Hence, liver tissue was obtained by needle sampling or open biopsy and RNA extracted from liver was analyzed.

RESULTS:

Complex rearrangements of the OTC transcript (three insertions and two deletions) were found in all five patients.

CONCLUSION:

In patients with a strong suspicion of OTC deficiency despite normal results of sequencing exonic regions of the OTC gene, characterization of liver OTC mRNA is highly effective in resolving the genotype. Liver tissue sampling by needle aspiration allows for both enzymatic analysis and RNA based diagnostics of OTC deficiency.

• Authors: Katharina Engel, Jean-Marc Nuoffer, Chris Mühlhausen, Vera Klaus, Carlo R Largiadèr, Konstantinos Tsiakas, René Santer, Bendicht Wermuth, Johannes Häberle
• Journal: Molecular genetics and metabolism (Mol Genet Metab) Vol. 94 Issue 3 Pg. 292-7 (Jul 2008) ISSN: 1096-7206 [Electronic] United States
• PMID: 18440262 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Messenger
• Ornithine Carbamoyltransferase

Topics

• Base Sequence
• Child, Preschool
• DNA Mutational Analysis
• Female
• Genetic Testing (methods)
• Humans
• Infant
• Infant, Newborn
• Male
• Neonatal Screening (methods)
• Ornithine Carbamoyltransferase (analysis, genetics)
• Ornithine Carbamoyltransferase Deficiency Disease (diagnosis, genetics)
• RNA, Messenger (analysis)
• Sensitivity and Specificity