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.
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: Johannes Häberle; Nathalie Boddaert; Alberto Burlina; Anupam Chakrapani; Marjorie Dixon; Martina Huemer; Daniela Karall; Diego Martinelli; Pablo Sanjurjo Crespo; René Santer; Aude Servais; Vassili Valayannopoulos; Martin Lindner; Vicente Rubio; Carlo Dionisi-Vici Journal: Orphanet J Rare Dis Date: 2012-05-29 Impact factor: 4.123
Authors: Runjun D Kumar; Lindsay C Burrage; Jan Bartos; Saima Ali; Eric Schmitt; Sandesh C S Nagamani; Cynthia LeMons Journal: Mol Genet Metab Rep Date: 2021-01-08
Authors: Anath C Lionel; Gregory Costain; Nasim Monfared; Susan Walker; Miriam S Reuter; S Mohsen Hosseini; Bhooma Thiruvahindrapuram; Daniele Merico; Rebekah Jobling; Thomas Nalpathamkalam; Giovanna Pellecchia; Wilson W L Sung; Zhuozhi Wang; Peter Bikangaga; Cyrus Boelman; Melissa T Carter; Dawn Cordeiro; Cheryl Cytrynbaum; Sharon D Dell; Priya Dhir; James J Dowling; Elise Heon; Stacy Hewson; Linda Hiraki; Michal Inbar-Feigenberg; Regan Klatt; Jonathan Kronick; Ronald M Laxer; Christoph Licht; Heather MacDonald; Saadet Mercimek-Andrews; Roberto Mendoza-Londono; Tino Piscione; Rayfel Schneider; Andreas Schulze; Earl Silverman; Komudi Siriwardena; O Carter Snead; Neal Sondheimer; Joanne Sutherland; Ajoy Vincent; Jonathan D Wasserman; Rosanna Weksberg; Cheryl Shuman; Chris Carew; Michael J Szego; Robin Z Hayeems; Raveen Basran; Dimitri J Stavropoulos; Peter N Ray; Sarah Bowdin; M Stephen Meyn; Ronald D Cohn; Stephen W Scherer; Christian R Marshall Journal: Genet Med Date: 2017-08-03 Impact factor: 8.822