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Aspartylglycosaminuria in the Finnish population: Identification of two point mutations in the heavy chain of glycoasparaginase

Mononen, Ilkka and Heisterkamp, Nora and Kaartinen, Vesa and Williams, Julian C. and Yates, John R., III and Griffin, Patrick R. and Hood, Leroy E. and Groffen, John (1991) Aspartylglycosaminuria in the Finnish population: Identification of two point mutations in the heavy chain of glycoasparaginase. Proceedings of the National Academy of Sciences of the United States of America, 88 (7). pp. 2941-2945. ISSN 0027-8424. PMCID PMC51356. doi:10.1073/pnas.88.7.2941.

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Aspartylglycosaminuria is an inherited lysosomal storage disease caused by deficiency of glycoasparaginase (EC and occurs with higher frequency among Finns than other populations. We have purified human glycoasparaginase and determined about 90% of the amino acid sequence of its light subunit and >70% of that of its heavy subunit by Edman degradation and mass spectrometry. Additional sequence data were obtained from the cloning and subsequent nucleotide analysis of a cDNA corresponding to the normal human glycoasparaginase gene. The enzyme is encoded by a single mRNA as a single polypeptide that is posttranslationally processed to generate the subunits and is glycosylated. After preparing first-strand cDNA from leukocyte and fibroblast total RNA, we used the polymerase chain reaction to amplify the glycoasparaginase cDNA of eight Finnish aspartylglycosaminuria patients. We demonstrate that the Finnish patients' mRNA sequence differed from the normal sequence by two single-base changes six nucleotides apart from one another in the heavy chain of glycoasparaginase. The first change resulted in the replacement of arginine by glutamine (R161Q), whereas the second change resulted in a cysteine to serine substitution (C163S). Both mutations resulted in novel restriction endonuclease sites and were present in all eight Finnish aspartylglycosaminuria patients originating from different pedigrees, but they were absent from Finnish and non-Finnish controls and a non-Finnish case of aspartylglycosaminuria. These results indicate molecular homogeneity in aspartylglycosaminuria alleles in the Finnish population.

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Hood, Leroy E.0000-0001-7158-3678
Additional Information:© 1991 National Academy of Sciences. Contributed by Leroy E. Hood, December 26, 1990. We thank Drs. M. Kaski, K. Raty, and E. Airaksinen for providing several of the Finnish aspartylglycosaminuria samples. We thank Drs. Joanne ten Hoeve, Q.-L. Hao, and Q.-S. Zhu for assistance; Dr. John Tomich and Bing Cai for the synthesis of oligonucleotides used in this study; and Ke-Cheng Chen for artwork.
Issue or Number:7
PubMed Central ID:PMC51356
Record Number:CaltechAUTHORS:20141217-095027032
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Official Citation:Aspartylglycosaminuria in the Finnish population: identification of two point mutations in the heavy chain of glycoasparaginase. I Mononen, N Heisterkamp, V Kaartinen, J C Williams, J R Yates, 3rd, P R Griffin, L E Hood, and J Groffen PNAS 1991 88 (7) 2941-2945; doi:10.1073/pnas.88.7.2941
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:52945
Deposited By: Ruth Sustaita
Deposited On:17 Dec 2014 18:00
Last Modified:10 Nov 2021 19:45

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