Engel Katharina, Nuoffer Jean-Marc, Mühlhausen Chris, Klaus Vera, Largiadèr Carlo R, Tsiakas Konstantinos, Santer René, Wermuth Bendicht, Häberle Johannes
Universitätsklinikum Münster, Klinik und Poliklinik für Kinder- und Jugendmedizin, Albert-Schweitzer-Strasse 33, 48149 Münster, Germany.
Mol Genet Metab. 2008 Jul;94(3):292-7. doi: 10.1016/j.ymgme.2008.03.009. Epub 2008 Apr 25.
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.
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.
Complex rearrangements of the OTC transcript (three insertions and two deletions) were found in all five patients.
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.
鸟氨酸转氨甲酰酶（OTC）缺乏症是尿素代谢中最常见的先天性错误，可导致高氨血症危象和乳清酸尿症。迄今为止，已描述了OTC基因内总共341个致病突变。然而，在约20%经酶学证实为OTC缺乏症的患者中，对OTC基因的外显子和相邻内含子片段进行基因组DNA测序时，未检测到突变。
对来自五个家庭的五名连续患者进行OTC基因的标准基因组DNA分析，未发现突变。因此，通过针吸活检或开放活检获取肝组织，并对从肝脏提取的RNA进行分析。
在所有五名患者中均发现了OTC转录本的复杂重排（三个插入和两个缺失）。
对于尽管OTC基因外显子区域测序结果正常但高度怀疑为OTC缺乏症的患者，肝脏OTC mRNA的特征分析在解析基因型方面非常有效。通过针吸进行肝组织采样可同时进行OTC缺乏症的酶学分析和基于RNA的诊断。
