Application of Next Generation Sequencing Genetic Studies of Urea Cycle Disorders
Main Article Content
Abstract
Urea cycle disorder is a group of rare, inherited metabolic disorders in the pathway transforming ammonia to urea. The mutations in genes coding for 6 enzymes that are participated including carbamoyl phosphate synthase I (CPSI), ornithine transcarbamylase (OTC), argininosuccinate synthase (ASS1), argininosuccinate lyase (ASL), arginase (ARG1), and N-acetyl glutamate synthase (NAGS), and 2 transport systems ((ornithine translocase (ONT1), citrin)) in the urea cycle are responsible for ammonia accumulation in the blood. Hyperammonemia is the cause of severe neurological symptoms and even death. In almost all cases, clinical examinations and biochemical experiments are necessary, but insufficient information for an accurate diagnosis. Mutation analysis is an effective method to confirm the diagnosis and could be the basis for genetic counseling. The rapid development and widely using of next generation sequencing (NGS) have brought incredible advances in molecular diagnosis of genetic diseases in general. In this article, we systematize the UCD genetic studies applying NGS method, thereby providing a basis for not only disease diagnosis but also future research
Keywords:
Genetic Diseases; Mutations; Next Generation Sequencing (NGS); Urea Cycle Disorder (UCD); Variantions
References
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[16] U. Amstutz, G. Andrey-Zurcher, D. Suciu, R. Jaggi, J. Haberle, C. R. Largiader, Sequence Capture and Next-generation Resequencing of Multiple Tagged Nucleic Acid Samples for Mutation Screening of Urea Cycle Disorders, Clin Chem, Vol. 57, No. 1, 2011, pp. 102-111. https://doi.org/10.1373/clinchem.2010.150706.
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https://doi.org/10.1016/j.cca.2019.12.022.
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[23 ] K. J. Park, S. Park, E. Lee, J. H. Park, J. H. Park, H. D. Park, S. Y. Lee, J. W. Kim, A Population-Based Genomic Study of Inherited Metabolic Diseases Detected Through Newborn Screening, Ann Lab Med., Vol. 36, No. 6, 2016, pp. 561-572.
https://doi.org/10.3343/alm.2016.36.6.561.
[24] V. Chongsrisawat, P. Damrongphol, C Ittiwut, R Ittiwut, K Suphapeetiporn, V Shotelersuk, The Phenotypic and Mutational Spectrum of Thai Female Patients with Ornithine Transcarbamylase Deficiency, Gene, Vol. 679, 2018, pp. 377-381.
https://doi.org/10.1016/j.gene.2018.09.026.
[25] E. H. Al Kaabi, A. W. El-Hattab, N-Acetylglutamate Synthase Deficiency: Novel Mutation Associated with Neonatal Presentation and Literature Review of Molecular and Phenotypic Spectra, Mol Genet Metab Rep., Vol. 8, 2016, pp. 94-98. https://doi.org/10.1016/j.ymgmr.2016.08.004.
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