Argininosuccinate lyase deficiency: mutational spectrum in Italian patients and identification of a novel ASL pseudogene - PubMed

Affiliations

• PMID: 17326097
• DOI: 10.1002/humu.20498

Argininosuccinate lyase deficiency: mutational spectrum in Italian patients and identification of a novel ASL pseudogene

Eva Trevisson et al. Hum Mutat. 2007 Jul.

Abstract

Argininosuccinic aciduria (ASAuria) is an inborn error of metabolism caused by mutations in the argininosuccinate lyase (ASL) gene, which leads to the accumulation of argininosuccinic acid (ASA) in body fluids and severe hyperammonemia. A severe neonatal form and a milder late-onset variant are described. We report a novel ASL pseudogene located in the centromeric region of chromosome 7, 14 novel mutations in the ASL gene, and a novel intronic polymorphism found in a cohort of Italian patients. Our approach relied exclusively on genomic DNA analysis. We found seven missense mutations, two nonsense, three small insertions/deletions, and two splicing mutations. Only two patients harbored previously described mutations, and among the novel variants only two were present in more than one kindred. The pathogenicity of the splicing mutations was demonstrated by a functional splicing assay that employed a hybrid minigene. We also performed molecular modeling using the reported three-dimensional structure of ASL to predict the functional consequences of the missense mutations. There was no genotype-phenotype correlation. Patients with neonatal onset display developmental delay and seizures despite adequate metabolic control. Moreover, hepatomegaly, fibrosis, and abnormal liver function tests are common complications in these patients, but not in patients with the late infancy form. We stress the importance of mutation analysis in patients with ASAuria, to confirm the clinical diagnosis, and to perform DNA-based prenatal diagnosis in future pregnancies of these families.

Similar articles

• Argininosuccinate lyase (ASL) deficiency: mutation analysis in 27 patients and a completed structure of the human ASL gene.

  Linnebank M, Tschiedel E, Häberle J, Linnebank A, Willenbring H, Kleijer WJ, Koch HG. Linnebank M, et al. Hum Genet. 2002 Oct;111(4-5):350-9. doi: 10.1007/s00439-002-0793-4. Epub 2002 Aug 14. Hum Genet. 2002. PMID: 12384776

• Identification of 16 novel mutations in the argininosuccinate synthetase gene and genotype-phenotype correlation in 38 classical citrullinemia patients.

  Gao HZ, Kobayashi K, Tabata A, Tsuge H, Iijima M, Yasuda T, Kalkanoglu HS, Dursun A, Tokatli A, Coskun T, Trefz FK, Skladal D, Mandel H, Seidel J, Kodama S, Shirane S, Ichida T, Makino S, Yoshino M, Kang JH, Mizuguchi M, Barshop BA, Fuchinoue S, Seneca S, Zeesman S, Knerr I, Rodés M, Wasant P, Yoshida I, De Meirleir L, Abdul Jalil M, Begum L, Horiuchi M, Katunuma N, Nakagawa S, Saheki T. Gao HZ, et al. Hum Mutat. 2003 Jul;22(1):24-34. doi: 10.1002/humu.10230. Hum Mutat. 2003. PMID: 12815590

• Alport syndrome. Molecular genetic aspects.

  Hertz JM. Hertz JM. Dan Med Bull. 2009 Aug;56(3):105-52. Dan Med Bull. 2009. PMID: 19728970

• Novel mutations in epithelial sodium channel (ENaC) subunit genes and phenotypic expression of multisystem pseudohypoaldosteronism.

  Edelheit O, Hanukoglu I, Gizewska M, Kandemir N, Tenenbaum-Rakover Y, Yurdakök M, Zajaczek S, Hanukoglu A. Edelheit O, et al. Clin Endocrinol (Oxf). 2005 May;62(5):547-53. doi: 10.1111/j.1365-2265.2005.02255.x. Clin Endocrinol (Oxf). 2005. PMID: 15853823 Review.

• Mutations and polymorphisms in the human argininosuccinate synthetase (ASS1) gene.

  Engel K, Höhne W, Häberle J. Engel K, et al. Hum Mutat. 2009 Mar;30(3):300-7. doi: 10.1002/humu.20847. Hum Mutat. 2009. PMID: 19006241 Review.

Cited by

• Regulation of intermediary metabolism by protein acetylation.

  Guan KL, Xiong Y. Guan KL, et al. Trends Biochem Sci. 2011 Feb;36(2):108-16. doi: 10.1016/j.tibs.2010.09.003. Epub 2010 Oct 8. Trends Biochem Sci. 2011. PMID: 20934340 Free PMC article. Review.

• Nitric-oxide supplementation for treatment of long-term complications in argininosuccinic aciduria.

  Nagamani SC, Campeau PM, Shchelochkov OA, Premkumar MH, Guse K, Brunetti-Pierri N, Chen Y, Sun Q, Tang Y, Palmer D, Reddy AK, Li L, Slesnick TC, Feig DI, Caudle S, Harrison D, Salviati L, Marini JC, Bryan NS, Erez A, Lee B. Nagamani SC, et al. Am J Hum Genet. 2012 May 4;90(5):836-46. doi: 10.1016/j.ajhg.2012.03.018. Epub 2012 Apr 26. Am J Hum Genet. 2012. PMID: 22541557 Free PMC article.

• Physical, cognitive, and social status of patients with urea cycle disorders in Japan.

  Kido J, Matsumoto S, Ito T, Hirose S, Fukui K, Kojima-Ishii K, Mushimoto Y, Yoshida S, Ishige M, Sakai N, Nakamura K. Kido J, et al. Mol Genet Metab Rep. 2021 Feb 7;27:100724. doi: 10.1016/j.ymgmr.2021.100724. eCollection 2021 Jun. Mol Genet Metab Rep. 2021. PMID: 33614409 Free PMC article.

• Regulation of cellular metabolism by protein lysine acetylation.

  Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL. Zhao S, et al. Science. 2010 Feb 19;327(5968):1000-4. doi: 10.1126/science.1179689. Science. 2010. PMID: 20167786 Free PMC article.

• NGS in argininosuccinic aciduria detects a mutation (D145G) which drives alternative splicing of ASL: a case report study.

  Wen W, Yin D, Huang F, Guo M, Tian T, Zhu H, Yang Y. Wen W, et al. BMC Med Genet. 2016 Feb 3;17:9. doi: 10.1186/s12881-016-0273-7. BMC Med Genet. 2016. PMID: 26843370 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Ovid Technologies, Inc.
  • Wiley

• Other Literature Sources

  • The Lens - Patent Citations Database

• Molecular Biology Databases

  • GlyGen glycoinformatics resource
  • The Weizmann Institute of Science GeneCards and MalaCards databases