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

Engel, Katharina; Nuoffer, Jean-Marc; Mühlhausen, Chris; Klaus, Vera; Largiadèr, Carlo R; Tsiakas, Konstantinos; Santer, René; Wermuth, Bendicht; Häberle, Johannes (2008). Analysis of mRNA transcripts improves the success rate of molecular genetic testing in OTC deficiency. Molecular genetics and metabolism, 94(3), pp. 292-7. Amsterdam: Elsevier 10.1016/j.ymgme.2008.03.009

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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.

Item Type:	Journal Article (Further Contribution)
Division/Institute:	04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine 04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry
UniBE Contributor:	Nuoffer, Jean-Marc, Largiadèr, Carlo Rodolfo, Wermuth, Bendicht
ISSN:	1096-7192
ISBN:	18440262
Publisher:	Elsevier
Language:	English
Submitter:	Anette van Dorland
Date Deposited:	04 Oct 2013 15:03
Last Modified:	05 Dec 2022 14:19
Publisher DOI:	10.1016/j.ymgme.2008.03.009
PubMed ID:	18440262
Web of Science ID:	000257225700004
URI:	https://boris.unibe.ch/id/eprint/27227 (FactScience: 105085)