Cloning of the human aspartoacylase cDNA and a common missense mutation in Canavan disease
Abstract
Canavan disease, an autosomal recessive leukodystrophy, is caused by deficiency of aspartoacylase and accumulation of N-acetylaspartic acid in brain. We have cloned the human aspartoacylase (ASP) cDNA spanning 1,435 basepairs, and show that the isolated cDNA expresses aspartoacylase activity in bacteria. Furthermore, an A to C base change, at nucleotide 854, has been found in 85% of the 34 Canavan alleles tested so far. This base change results in a missense Glu285Ala mutation that is predicted to be part of the catalytic domain of aspartoacylase. The data suggest that the catalytic centre of aspartoacylase involves a triad of Ser, His and Glu residues. Our findings have implications for diagnosis and screening of Canavan disease.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Canavan disease is caused by inherited mutations in the gene encoding for the enzyme aspartoacylase (ASPA), which results in the accumulation of its substrate, N-acetylaspartate (NAA).
“Canavan disease is caused by inherited mutations in the gene encoding for the enzyme aspartoacylase (ASPA)10 which results in the accumulation of its substrate, N-acetylaspartate (NAA).”
From Preclinical biodistribution, tropism, and efficacy of oligotropic AAV/Olig001 in a mouse model of congenital white matter disease (2021) · cites this paper as [10]
Cites
PROTEIN MEASUREMENT WITH THE FOLIN PHENOL REAGENT
Lowry, O. H., Rosebrough, N., Farr, A. L., & Randall, R. (1951) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)52451-6 · Cited by 315,771 · see citing works
Molecular Cloning: A Laboratory Manual
Sambrook, J., Fritsch, E., & Maniatis, T. (1989) · UCLA - Biblioteca de Ciencias de la Salud · Cited by 133,589 · see citing works
Molecular cloning: A laboratory manual
Deininger, P. L. (1990) · Analytical Biochemistry · doi:10.1016/0003-2697(90)90595-z · Cited by 84,684 · see citing works
DNA sequencing with chain-terminating inhibitors
Sanger, F., Nicklen, S., & Coulson, A. R. (1977) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.74.12.5463 · Cited by 68,572 · see citing works
Single-Step Method of RNA Isolation by Acid Guanidinium Thiocyanate–Phenol–Chloroform Extraction
Chomczynski, P., & Sacchi, N. (1987) · Analytical Biochemistry · doi:10.1006/abio.1987.9999 · Cited by 65,240 · see citing works
Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction
Chomczyński, P., & Sacchi, N. (1987) · Analytical Biochemistry · doi:10.1016/0003-2697(87)90021-2 · Cited by 47,092 · see citing works
A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity
Feinberg, A. P., & Vogelstein, B. (1983) · Analytical Biochemistry · doi:10.1016/0003-2697(83)90418-9 · Cited by 24,512 · see citing works
Saiki, R. K., Scharf, S., Faloona, F., Mullis, K. B., Horn, G. T., Erlich, H. A., & Arnheim, N. (1985) · Science · doi:10.1126/science.2999980 · Cited by 8,956 · see citing works
A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity
(1984) · Analytical Biochemistry · doi:10.1016/0003-2697(84)90381-6 · Cited by 4,950 · see citing works
Orita, M., Suzuki, Y., Sekiya, T., & Hayashi, K. (1989) · Genomics · doi:10.1016/0888-7543(89)90129-8 · Cited by 3,433 · see citing works
3′ Non-coding region sequences in eukaryotic messenger RNA
Proudfoot, N. J., & Brownlee, G. G. (1976) · Nature · doi:10.1038/263211a0 · Cited by 3,021 · see citing works
Transcription termination and 3′ processing: the end is in site!
Birnstiel, M. L., Busslinger, M., & Strub, K. (1985) · Cell · doi:10.1016/s0092-8674(85)80007-6 · Cited by 1,477 · see citing works
Birken, D. L., & Oldendorf, W. H. (1989) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(89)80048-x · Cited by 783 · see citing works
Saiki, R. K., Scharf, S., Faloona, F., Mullis, K. B., Horn, G. T., Erlich, H. A., & Arnheim, N. (1992) · PubMed · Cited by 733 · see citing works
Cygler, M., Schrag, J. D., Sussman, J. L., Harel, M., Silman, I., Gentry, M. K., & Doctor, B. P. (1993) · Protein Science · doi:10.1002/pro.5560020309 · Cited by 565 · see citing works
Urenjak, J., Williams, S. R., Gadian, D. G., & Noble, M. (1992) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1992.tb08875.x · Cited by 503 · see citing works
Aspartoacylase deficiency and N‐acetylaspartic aciduria in patients with canavan disease
Matalon, R. K., Michals, K., Sebesta, D. G., Deanching, M., Gashkoff, P., Casanova, J., Optiz, J. M., & Reynolds, J. F. (1988) · American Journal of Medical Genetics · doi:10.1002/ajmg.1320290234 · Cited by 405 · see citing works
Self-citationSPECIFICITY OF AMINO ACID ACYLASES
Birnbaum, S. M., Levintow, L., Kingsley, R. B., & Greenstein, J. P. (1952) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)55898-1 · Cited by 350 · see citing works
Immunohistochemical localization of N-acetylaspartate in rat brain
Moffett, J. R., Namboodiri, M. A. A., Cangro, C. B., & Neale, J. H. (1991) · Neuroreport · doi:10.1097/00001756-199103000-00005 · Cited by 335 · see citing works
N-ACETYL-l-ASPARTIC ACID IN BRAIN
Tallan, H. H., Moore, S., & Stein, W. H. (1956) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)65789-8 · Cited by 328 · see citing works
Meyerhoff, D. J., MacKay, S., Bachman, L., Poole, N., Dillon, W. P., Weiner, M. W., & Fein, G. (1993) · Neurology · doi:10.1212/wnl.43.3_part_1.509 · Cited by 197 · see citing works
Gideon, P., Henriksen, O. M., Sperling, B. K., Christiansen, P., Olsen, T. S., Jørgensen, H. S., & Arlien-Søborg, P. (1992) · Stroke · doi:10.1161/01.str.23.11.1566 · Cited by 179 · see citing works
Grodd, W., Krägeloh‐Mann, I., Klose, U., et al. (1991) · Radiology · doi:10.1148/radiology.181.1.1887030 · Cited by 173 · see citing works
SCHILDER'S ENCEPHALITIS PERIAXIALIS DIFFUSA
Canavan, M. M. (1931) · Archives of Neurology And Psychiatry · doi:10.1001/archneurpsyc.1931.02230020085005 · Cited by 145 · see citing works
Moffett, J. R., Namboodiri, M., & Neale, J. (1993) · Journal of Histochemistry and Cytochemistry · doi:10.1177/41.4.8450195 · Cited by 125 · see citing works
Grodd, W., Krägeloh‐Mann, I., Petersen, D., et al. (1990) · The Lancet · doi:10.1016/0140-6736(90)91982-g · Cited by 117 · see citing works
Immunohistochemistry and Biosynthesis of N‐Acetylaspartylglutamate in Spinal Sensory Ganglia
Cangro, C. B., Namboodiri, M. A. A., Sklar, L. A., et al. (1987) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1987.tb01030.x · Cited by 116 · see citing works
Purification, Characterization, and Localization of Aspartoacylase from Bovine Brain
Kaul, R., Casanova, J., Johnson, T., Tang, P., & Matalon, R. K. (1991) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1991.tb02571.x · Cited by 109 · see citing works
Self-citationStudies on the Role of N-Acetylaspartic Acid in Mammalian Brain
Jacobson, K. B. (1959) · The Journal of General Physiology · doi:10.1085/jgp.43.2.323 · Cited by 93 · see citing works
Amino acid sequence of the N alpha-terminal 201 residues of human erythrocyte membrane band 3.
Kaul, R., Murthy, S. N. P., Reddy, A. G., et al. (1983) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(20)82016-x · Cited by 89 · see citing works
Self-citationSTUDIES ON THE FUNCTION OF N‐ACETYL ASPARTIC ACID IN BRAIN
McIntosh, J. C., & Cooper, J. R. (1965) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1965.tb10267.x · Cited by 87 · see citing works
PROGRESSIVE DEGENERATIVE SUBCORTICAL ENCEPHALOPATHY
GLOBUS, J. H. (1928) · Archives of Neurology And Psychiatry · doi:10.1001/archneurpsyc.1928.02210180041003 · Cited by 85 · see citing works
Aspartoacylase Deficiency: The Enzyme Defect in Canavan Disease
Matalon, R. K., Kaul, R., Casanova, J., Michals, K., Johnson, T., Rapin, I., Gashkoff, P., & Deanching, M. (1989) · Journal of Inherited Metabolic Disease · doi:10.1007/bf03335413 · Cited by 84 · see citing works
Self-citationThe Enzymatic Synthesis of N-Acetyl-L-aspartic Acid by Subcellular Preparations of Rat Brain
Goldstein, F. B. (1969) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)36410-4 · Cited by 79 · see citing works
Cerebral spongy degeneration of infancy
Adornato, B. T., O’Brien, J. S., Lampert, P. W., et al. (1972) · Neurology · doi:10.1212/wnl.22.2.202 · Cited by 74 · see citing works
Ory‐Lavollée, L., Blakely, R., & Coyle, J. T. (1987) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1987.tb05601.x · Cited by 72 · see citing works
Biosynthesis of N-Acetyl-l-aspartic Acid
Goldstein, F. B. (1959) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)69763-7 · Cited by 65 · see citing works
Canavan disease: Biochemical and molecular studies
Matalon, R. K., Kaul, R., & Michals, K. (1993) · Journal of Inherited Metabolic Disease · doi:10.1007/bf00711906 · Cited by 65 · see citing works
Self-citationTermination of the ovalbumin gene transcription.
LeMeur, M., Galliot, B., & GERLINGER, P. (1984) · The EMBO Journal · doi:10.1002/j.1460-2075.1984.tb02209.x · Cited by 62 · see citing works
Electron miscroscopic and enzyme histochemical studies of the cerebellum in spongy degeneration
Adachi, M., Torii, J., Schneck, L., et al. (1972) · Acta Neuropathologica · doi:10.1007/bf00687899 · Cited by 58 · see citing works
Birnbaum, S. M. (1955) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(55)02176-9 · Cited by 54 · see citing works
[Schilder's encephalitis periaxialis diffusa].
Klimkova, E., & Fantis, A. (1950) · PubMed · Cited by 51 · see citing works
Aspartoacylase deficiency and Canavan disease in Saudi Arabia
Ozand, P. T., Gascon, G. G., & Dhalla, M. (1990) · American Journal of Medical Genetics · doi:10.1002/ajmg.1320350224 · Cited by 50 · see citing works
Shigematsu, H., Okamura, N., Shimeno, H., et al. (1983) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1983.tb08052.x · Cited by 48 · see citing works
Decreased brain N-acetylaspartate in Huntington's disease
Dunlop, D. S., Hale, D. M. M., & Lajtha, Á. (1992) · Brain Research · doi:10.1016/0006-8993(92)90925-y · Cited by 46 · see citing works
A new case of holocarboxylase synthetase deficiency
Briones, P., Ribes, A., Vilaseca, M., Rodríguez‐Valcárcel, G., Thuy, L. P., & Sweetman, L. (1989) · Journal of Inherited Metabolic Disease · doi:10.1007/bf01799228 · Cited by 35 · see citing works
Miller, Y. E., Drabkin, H. A., Jones, C., et al. (1990) · Genomics · doi:10.1016/0888-7543(90)90237-o · Cited by 31 · see citing works
Prenatal diagnosis of canavan disease
Matalon, R. K., Michals, K., Gashkoff, P., et al. (1992) · Journal of Inherited Metabolic Disease · doi:10.1007/bf02435985 · Cited by 27 · see citing works
Self-citationIsolation and characterization of human blood-coagulation factor X cDNA
Kaul, R., Hildebrand, B., Roberts, S., et al. (1986) · Gene · doi:10.1016/0378-1119(86)90112-5 · Cited by 23 · see citing works
Self-citationCanavan disease: findings in four new cases
Michelakakis, H., Giouroukos, S., Divry, P., et al. (1991) · Journal of Inherited Metabolic Disease · doi:10.1007/bf01800603 · Cited by 14 · see citing works
Decrease in N‐Acetyl‐ l ‐Aspartic Acid in Brain of Myodystrophic Mice
Marcucci, F., Colombo, L., Ponte, G. D., et al. (1984) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1984.tb05412.x · Cited by 13 · see citing works
Bell, J. D., Cox, I. J., Williams, S., et al. (1991) · Journal of General Virology · doi:10.1099/0022-1317-72-10-2419 · Cited by 13 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Long-term follow-up after gene therapy for canavan disease
Leone, P., Shera, D., McPhee, S. W. J., Francis, J. S., Kolodny, E. H., Bilaniuk, L. T., Wang, D.-J., Assadi, M., Goldfarb, O., Goldman, H. W., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3003454 · Cited by 307 · see citing works
Immune responses to AAV in a phase I study for Canavan disease
McPhee, S. W. J., Janson, C. G., Li, C., Samulski, R. J., Camp, A. S., Francis, J., Shera, D., Lioutermann, L., Feely, M., Freese, A., et al. (2006) · The Journal of Gene Medicine · doi:10.1002/jgm.885 · Cited by 241 · see citing works
Viral vectors for therapy of neurologic diseases
Choudhury, S. R., Hudry, E., Maguire, C. A., Sena-Esteves, M., Breakefield, X. O., & Grandi, P. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2016.02.013 · Cited by 190 · see citing works
Topçu, M., Jobard, F., Halliez, S., Coskun, T., Yalçinkayal, C., Gerceker, F. O., Wanders, R. J. A., Prud'homme, J.-F., Lathrop, M., Özguc, M., et al. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh300 · Cited by 133 · see citing works
Traka, M., Wollmann, R. L., Cerda, S. R., Dugas, J., Barres, B. A., & Popko, B. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.1490-08.2008 · Cited by 82 · see citing works
Clinical Applications Involving CNS Gene Transfer
Kantor, B., McCown, T., Leone, P., & Gray, S. J. (2014) · Advances in Genetics · doi:10.1016/b978-0-12-800149-3.00002-0 · Cited by 74 · see citing works
Gessler, D. J., Li, D., Xu, H., Su, Q., Sanmiguel, J., Tuncer, S., Moore, C., King, J., Matalon, R., & Gao, G. (2017) · JCI Insight · doi:10.1172/jci.insight.90807 · Cited by 70 · see citing works
Self-citationFrancis, J. S., Markov, V., Wojtas, I. D., Gray, S., McCown, T., Samulski, R. J., Figueroa, M., & Leone, P. (2021) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2021.01.009 · Cited by 41 · see citing works
Aspartoacylase supports oxidative energy metabolism during myelination
Francis, J. S., Strande, L., Markov, V., & Leone, P. (2012) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2012.66 · Cited by 41 · see citing works
Ahmed, S. S., Schattgen, S. A., Frakes, A. E., Sikoglu, E. M., Su, Q., Li, J., Hampton, T. G., Denninger, A. R., Kirschner, D. A., Kaspar, B., et al. (2016) · Molecular Therapy · doi:10.1038/mt.2016.68 · Cited by 24 · see citing works
Self-citationEndogenous aspartoacylase expression is responsive to glutamatergic activity in vitro and in vivo
Francis, J. S., Strande, L., Pu, A., & Leone, P. (2011) · Glia · doi:10.1002/glia.21187 · Cited by 12 · see citing works
- Authors
- Kaul, R., Ping Gao, G., Balamurugan, K., & Matalon, R.
- Affiliations
- Miami Children's Hospital (US)
- ORCID
- Kaul, Rajinder
- Venue
- Nature Genetics
- Published
- 1993-10
- Volume
- 5
- Issue
- 2
- Pages
- 118-123
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2024102509
- Cited by
- 221
- References
- 52
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 7 · 2023: 4 · 2022: 1 · 2021: 1 · 2020: 5 · 2019: 5 · 2017: 4 · 2016: 11 · 2015: 8 · 2014: 13 · 2013: 10 · 2012: 10
- FWCI
- 5.09
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Keywords
- Canavan disease, aspartoacylase, cDNA cloning, missense mutations, leukodystrophy, N-acetylaspartic acid, catalytic domain, enzyme deficiency, disease screening
- MeSH terms
- Amidohydrolases, Amino Acid Sequence, Animals, Base Sequence, Cattle, Humans, Molecular Sequence Data, Mutation, Sequence Alignment, Canavan Disease, DNA, Complementary
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
