Eight novel ABCD1 gene mutations and three polymorphisms in patients with X-linked adrenoleukodystrophy: The first polymorphism causing an amino acid exchange
Abstract
X-ALD is a neurological disorder associated with inherited defects in the ABCD1 (ALD) gene located on Xq28 and with impaired peroxisomal very long-chain fatty acid beta-oxidation. We examined the ABCD1 gene in probands from 11 unrelated X-ALD Czech and Slovak families by the direct sequencing of cDNA or genomic PCR products. In 10 families there were 10 different mutations, eight of which were novel. The spectrum of mutations consists of six point mutations, three microdeletions (1bp, 2bp, 4 bp), and one large deletion (229bp). In the 11th family we detected two novel single-base pair substitutions in exon 1 (c.38 A>C and c.649 A>G), both causing amino acid exchanges (N13T and K217E). Expression studies revealed that only K217E is a deleterious mutation, because a plasmid encoding ALDP with K217E was ineffective in the restoration of defective beta-oxidation in X-ALD fibroblasts. The N13T amino acid exchange, on the other hand, did not affect ALDP function. Thus, N13T represents the first polymorphism causing an amino acid exchange in the ABCD1 gene. As this polymorphism was observed neither in 100 control alleles nor in 300 X-ALD patients who have been sequenced so far world-wide, it seems to be very rare or unique. Two additional novel polymorphisms were found by the sequencing of the ABCD1 gene from our patients: c.-59 C/T in the 5'untranslated region and c.2019 C/T (F673F) in exon 10. The frequencies of these two polymorphisms, were 11/150 and 2/150 control alleles, respectively.
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?
p.Gly608Asp was reported as the pathogenic variant in an ALD male patient, but gnomAD data show its frequency to be 124/162246 alleles, confirming that it is not a pathogenic variant.
“For example, p.Gly608Asp was reported as the pathogenic variant in an ALD male patient (Database Ref 48) [26], but data from gnomAD show its frequency to be 124/162246 alleles (X:153008483 G/A), confirming that this is not a pathogenic variant.”
From Structure and Function of the ABCD1 Variant Database: 20 Years, 940 Pathogenic Variants, and 3400 Cases of Adrenoleukodystrophy (2022) · cites this paper as [26]
The mutation c.1823 G>A in exon 8 of ABCD1 was previously shown to cause X-ALD, as it was found in the ABCD1 coding sequence in different patients.
“However, in a previous study, this mutation was clearly shown to cause X-ALD, as it was found in the ABCD1 coding sequence in different patients.53”
From The genetic landscape of X-linked adrenoleukodystrophy: inheritance, mutations, modifier genes, and diagnosis (2015) · cites this paper as [53]
Cites
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
The Metabolic and Molecular Bases of Inherited Disease
Scriver, R. C. (1995) · Medical Entomology and Zoology · Cited by 12,101 · see citing works
The metabolic and molecular bases of inherited disease
Chen, Y.-T. (2001) · Medical Entomology and Zoology · Cited by 6,928 · see citing works
ABC Transporters: From Microorganisms to Man
Higgins, C. F. (1992) · Annual Review of Cell Biology · doi:10.1146/annurev.cb.08.110192.000435 · Cited by 3,985 · see citing works
Putative X-linked adrenoleukodystrophy gene shares unexpected homology with ABC transporters
Mosser, J., Douar, A.-M., Sarde, C.-O., Kioschis, P., Feil, R., Moser, H., Poustka, A.-M., Mandel, J.-L., & Aubourg, P. (1993) · Nature · doi:10.1038/361726a0 · Cited by 1,202 · see citing works
Nonsense-mediated mRNA decayin health and disease
Frischmeyer, P. A. (1999) · Human Molecular Genetics · doi:10.1093/hmg/8.10.1893 · Cited by 991 · see citing works
Adrenoleukodystrophy: phenotype, genetics, pathogenesis and therapy
Moser, H. (1997) · Brain · doi:10.1093/brain/120.8.1485 · Cited by 478 · see citing works
Moser, H. (1981) · doi:10.1212/wnl.31.10.1241 · Cited by 396 · see citing works
Soussi, T., Dehouche, K., & Béroud, C. (2000) · Human Mutation · doi:10.1002/(sici)1098-1004(200001)15:1 · Cited by 269 · see citing works
X-linked adrenoleukodystrophy: Genes, mutations, and phenotypes
Smith, K. D., Kemp, S., Braiterman, L. T., Lu, J.-F., Wei, H.-M., Geraghty, M., Stetten, G., Bergin, J. S., Pevsner, J., & Watkins, P. A. (1999) · Neurochemical Research · doi:10.1023/a:1022535930009 · Cited by 190 · see citing works
X linked adrenoleukodystrophy: clinical presentation, diagnosis, and therapy
van Geel, B. M., Assies, J., Wanders, R. J. A., & Barth, P. G. (1997) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.63.1.4 · Cited by 162 · see citing works
Netik, A., Forss-Petter, S., Holzinger, A., Molzer, B., Unterrainer, G., & Berger, J. (1999) · Human Molecular Genetics · doi:10.1093/hmg/8.5.907 · Cited by 148 · see citing works
Self-citationEichler, E. (1997) · Human Molecular Genetics · doi:10.1093/hmg/6.7.991 · Cited by 143 · see citing works
Spectrum of mutations in the gene encoding the adrenoleukodystrophy protein.
(1995) · Europe PMC (PubMed Central) · Cited by 130 · see citing works
PXA1, a possible Saccharomyces cerevisiae ortholog of the human adrenoleukodystrophy gene.
Shani, N., Watkins, P. A., & Valle, D. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.13.6012 · Cited by 129 · see citing works
Altered expression of ALDP in X-linked adrenoleukodystrophy.
(1995) · PubMed Central · Cited by 127 · see citing works
Berger, J., Molzer, B., Fae, I., & Bernheimer, H. (1994) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1994.2855 · Cited by 126 · see citing works
Self-citationAccurate DNA-Based Diagnostic and Carrier Testing for X-Linked Adrenoleukodystrophy
Boehm, C. D., Cutting, G. R., Lachtermacher, M. B., Moser, H. W., & Chong, S. S. (1999) · Molecular Genetics and Metabolism · doi:10.1006/mgme.1998.2779 · Cited by 112 · see citing works
Cartier, N., Lopez, J., Moullier, P., Rocchiccioli, F., Rolland, M. O., Jorge, P., Mosser, J., Mandel, J. L., Bougnères, P. F., & Danos, O. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.5.1674 · Cited by 105 · see citing works
Mutational analysis of patients with X-linked adrenoleukodystrophy
Kok, F., Neumann, S., Sarde, C.-O., Zheng, S., Wu, K.-H., Wei, H.-M., Bergin, J., Watkins, P. A., Gould, S., Sack, G., et al. (1995) · Human Mutation · doi:10.1002/humu.1380060203 · Cited by 103 · see citing works
(1996) · PubMed Central · Cited by 99 · see citing works
Identification of female carriers of adrenoleukodystrophy
Moser, H. W., Moser, A. E., Trojak, J. E., & Supplee, S. W. (1983) · The Journal of Pediatrics · doi:10.1016/s0022-3476(83)80775-6 · Cited by 99 · see citing works
Peroxisomal fatty acid β-oxidation in HepG2 cells
Watkins, P. A., Ferrell, E. V., Pedersen, J. I., & Hoefler, G. (1991) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(91)90419-j · Cited by 86 · see citing works
Genomic organization of the adrenoleukodystrophy gene
Sarde, C.-O., Mosser, J., Kioschis, P., Kretz, C., Vicaire, S., Aubourg, P., Poustka, A., & Mandel, J.-L. (1994) · Genomics · doi:10.1006/geno.1994.1339 · Cited by 82 · see citing works
Kemp, S., Ligtenberg, M. J. L., Vangeel, B. M., Barth, P. G., Wolterman, R. A., Schoute, F., Sarde, C. O., Mandel, J. L., Vanoost, B. A., & Bolhuis, P. A. (1994) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1994.1979 · Cited by 75 · see citing works
Characterization and Analysis of Conserved Motifs in a Peroxisomal ATP-binding Cassette Transporter
Shani, N., Sapag, A., & Valle, D. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.15.8725 · Cited by 61 · see citing works
Takano, H., Koike, R., Onodera, O., Sasaki, R., & Tsuji, S. (1999) · Archives of Neurology · doi:10.1001/archneur.56.3.295 · Cited by 58 · see citing works
Missense mutations are frequent in the gene for X-chromosomal adrenoleukodystrophy (ALD)
Fuchs, S., Sarde, C. O., Wedemann, H., Schwinger, E., Mandel, J. L., & Gal, A. (1994) · Human Molecular Genetics · doi:10.1093/hmg/3.10.1903 · Cited by 57 · see citing works
Topology of ATP-Binding Domain of Adrenoleukodystrophy Gene Product in Peroxisomes
Contreras, M., Sengupta, T. K., Sheikh, F. G., Aubourg, P. R., & Singh, I. (1996) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1996.0467 · Cited by 51 · see citing works
Mutations in the adrenoleukodystrophy gene
Dodd, A. W., Rowland, S. A., Hawkes, S. L. J., Kennedy, M. A., & Love, D. R. (1997) · Human Mutation · doi:10.1002/(sici)1098-1004(1997)9:6 · Cited by 47 · see citing works
Adrenoleukodystrophy: The Restoration of Peroxisomal β-Oxidaton by Transfection of Normal cDNA
Shinnoh, N., Yamada, T., Yoshimura, T., Furuya, H., Yoshida, Y., Suzuki, Y., Shimozawa, N., Orii, T., & Kobayashi, T. (1995) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1995.1733 · Cited by 43 · see citing works
Thyroid hemiagenesis and elevated thyrotropin levels in a child with Williams syndrome
Cammareri, V., Vignati, G., Nocera, G., Beck‐Peccoz, P., & Persani, L. (1999) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(19990827)85:5 · Cited by 41 · see citing works
Determination of 30 X-linked adrenoleukodystrophy mutations, including 15 not previously described
Lachtermacher, M., Seu�nez, H. N., Moser, A. B., Moser, H. W., & Smith, K. D. (2000) · Human Mutation · doi:10.1002/(sici)1098-1004(200004)15:4 · Cited by 36 · see citing works
Identification of a new frameshift mutation (1801delAG) in the ALD gene
Barceló, A., Girós, M., Sarde, C., Martínez-Bermejo, A., Mandel, J., Pàmpols, T., & Estivill, X. (1994) · Human Molecular Genetics · doi:10.1093/hmg/3.10.1889 · Cited by 27 · see citing works
Komaki, S., Matsuura, T., Oyanagi, K., Hoshide, R., Kiwaki, K., Endo, F., Shimadzu, M., & Matsuda, I. (1997) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(19970317)69:2 · Cited by 22 · see citing works
cDNA sequence of Aldgh, the mouse homolog of the X-linked adrenoleukodystrophy gene
Sarde, C., Thomas, J., Puccio, H. M., Garnier, J., & Mandel, J. (1994) · Mammalian Genome · doi:10.1007/bf00292021 · Cited by 19 · see citing works
Braun, A. D., Kammerer, S., Ambach, H., & Roscher, A. A. (1996) · Human Mutation · doi:10.1002/(sici)1098-1004(1996)7:2 · Cited by 16 · see citing works
Imamura, A., Suzuki, Y., Song, X., Fukao, T., Uchiyama, A., Shimozawa, N., Kamijo, K., Hashimoto, T., Orii, T., & Kondo, N. (1997) · Clinical Genetics · doi:10.1111/j.1399-0004.1997.tb02481.x · Cited by 15 · see citing works
Graham, G. E., MacLeod, P., Lillicrap, D., & Bridge, P. J. (1991) · Journal of Inherited Metabolic Disease · doi:10.1007/bf01800346 · Cited by 14 · see citing works
Korenke, G. C., Krasemann, E., Meier, V., Beuche, W., HUNNEMAN, D. H., & Hanefeld, F. A. (1998) · Human Mutation · doi:10.1002/humu.1380110166 · Cited by 9 · see citing works
Mutational analysis of adrenoleukodystrophy (ALD) gene in Japanese ALD patients
Koike, R., Onodera, O., & Tabe, H. (1994) · The American Journal of Human Genetics · Cited by 2 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Whole-Genome Sequencing in a Patient with Charcot–Marie–Tooth Neuropathy
Lupski, J. R., Reid, J. G., Gonzaga-Jauregui, C., Rio Deiros, D., Chen, D. C. Y., Nazareth, L., Bainbridge, M., Dinh, H., Jing, C., Wheeler, D. A., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa0908094 · Cited by 759 · see citing works
Kemp, S., Pujol, A., Waterham, H. R., van Geel, B. M., Boehm, C. D., Raymond, G. V., Cutting, G. R., Wanders, R. J. A., & Moser, H. W. (2001) · Human Mutation · doi:10.1002/humu.1227 · Cited by 332 · see citing works
X-linked adrenoleukodystrophy: Clinical, metabolic, genetic and pathophysiological aspects
Kemp, S., Berger, J., & Aubourg, P. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2012.03.012 · Cited by 283 · see citing works
Self-citationX-linked adrenoleukodystrophy: Clinical, biochemical and pathogenetic aspects
Berger, J., & Gärtner, J. (2006) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2006.07.010 · Cited by 199 · see citing works
Self-citationBerger, J., Wiesinger, C., & Eichler, F. (2015) · The Application of Clinical Genetics · doi:10.2147/tacg.s49590 · Cited by 140 · see citing works
Self-citationLupski, J., Gonzaga-Jauregui, C., Yang, Y.-P., Bainbridge, M., Jhangiani, S., Buhay, C., Kovar, C., Wang, M., Hawes, A., Reid, J., et al. (2013) · Genome Medicine · doi:10.1186/gm461 · Cited by 148 · see citing works
Paintlia, A. S., Gilg, A. G., Khan, M., Singh, A. K., Barbosa, E., & Singh, I. (2003) · Neurobiology of Disease · doi:10.1016/j.nbd.2003.08.013 · Cited by 120 · see citing works
Mallack, E. J., Gao, K., Engelen, M., & Kemp, S. (2022) · Cells · doi:10.3390/cells11020283 · Cited by 60 · see citing works
X-linked adrenoleukodystrophy: ABCD1 de novo mutations and mosaicism
Wang, Y., Busin, R., Reeves, C., Bezman, L., Raymond, G., Toomer, C. J., Watkins, P. A., Snowden, A., Moser, A., Naidu, S., et al. (2011) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2011.05.016 · Cited by 58 · see citing works
Coll, M., Palau, N., Camps, C., Ruíz, M., Pàmpols, T., & Girós, M. (2005) · Clinical Genetics · doi:10.1111/j.1399-0004.2005.00423.x · Cited by 42 · see citing works
ABCD1 Gene Mutations in Chinese Patients With X-Linked Adrenoleukodystrophy
Pan, H., Xiong, H., Wu, Y., Zhang, Y.-H., Bao, X., Jiang, Y.-W., & Wu, X. (2005) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2005.03.006 · Cited by 30 · see citing works
Guimarães, C. P., Lemos, M., Sá-Miranda, C., & Azevedo, J. E. (2002) · Molecular Genetics and Metabolism · doi:10.1016/s1096-7192(02)00023-9 · Cited by 20 · see citing works
Morita, M., Kobayashi, J., Yamazaki, K., Kawaguchi, K., Honda, A., Sugai, K., Shimozawa, N., Koide, R., & Imanaka, T. (2012) · JIMD Reports · doi:10.1007/8904_2012_209 · Cited by 15 · see citing works
Amorosi, C. A., Myšková, H., Monti, M. R., Argaraña, C. E., Morita, M., Kemp, S., de Kremer, R. D., Dvořáková, L., & Ramírez, A. M. O. (2012) · PLoS ONE · doi:10.1371/journal.pone.0052635 · Cited by 15 · see citing works
Schackmann, M. J. A., Ofman, R., van Geel, B. M., Dijkstra, I. M. E., van Engelen, K., Wanders, R. J. A., Engelen, M., & Kemp, S. (2016) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2016.03.009 · Cited by 15 · see citing works
Dong, B., Lv, W., Xu, L., Zhao, Y., Sun, X., Wang, Z., Cheng, B., Fu, Z., & Wang, Y. (2022) · International Journal of Endocrinology · doi:10.1155/2022/5479781 · Cited by 12 · see citing works
Peripheral neuropathies: Whole genome sequencing identifies causal variants in CMT
Züchner, S. (2010) · Nature Reviews Neurology · doi:10.1038/nrneurol.2010.108 · Cited by 15 · see citing works
Jia, M., Wu, W., Li, C., Cai, X., Zhang, L., Fang, Y., Zhu, C., & Gu, M. (2019) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2019.7804 · Cited by 8 · see citing works
Targeting Chemotherapy Resistance in Glioblastoma Through Modulation of ABC Transporters
Tivnan, A. (2016) · Resistance to targeted anti-cancer therapeutics · doi:10.1007/978-3-319-46505-0_2 · Cited by 3 · see citing works
Linking mutated primary structure of adrenoleukodystrophy protein with X-linked adrenoleukodystrophy
Yan, S., & Wu, G. (2010) · Computer Methods in Biomechanics & Biomedical Engineering · doi:10.1080/10255840903279974 · Cited by 3 · see citing works
Adrenoleukodystrophy: Molecular, Metabolic, Pathologic, and Therapeutic Aspects
Contreras, M. A., & Singh, I. (2008) · Springer eBooks · doi:10.1007/978-0-387-30375-8_2 · Cited by 2 · see citing works
Genetic Modulation of Vulnerable Plaques
Dong, C., & Goldschmidt‐Clermont, P. J. (2006) · doi:10.1002/9780470987575.ch25
Molecular Genetics of X‐linked Adrenoleukodystrophy
Kemp, S. (2014) · Wiley eBooks · doi:10.1002/9780470015902.a0024277
- Authors
- Dvoráková, L., Štorkánová, G., Unterrainer, G., Hujová, J., Kmoch, S., Zeman, J., Hrebícek, M., & Berger, J.
- Affiliations
- University of Vienna (AT)
- General University Hospital in Prague (CZ)
- Venue
- Human Mutation
- Publisher
- Hindawi Limited
- Published
- 2001-07
- Volume
- 18
- Issue
- 1
- Pages
- 52-60
- ISSN
- 1059-7794 (ISSN-L)
- 1098-1004
- OpenAlex
- W2034204538
- Cited by
- 23
- References
- 41
- Citations by year
- 2022: 2 · 2019: 1 · 2016: 2 · 2015: 1 · 2014: 1 · 2013: 1 · 2012: 3
- FWCI
- 0.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Mutation (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Keywords
- X-linked adrenoleukodystrophy, ABCD1 gene, novel mutations, microdeletion, point mutations, amino acid substitutions, 5' untranslated region polymorphism, mutation spectrum
- MeSH terms
- ATP Binding Cassette Transporter, Subfamily D, Member 1, Adolescent, Adrenoleukodystrophy, Adult, Alleles, Child, DNA Mutational Analysis, Exons, Fatty Acids, Female, Humans, Genetic Linkage, Male, Membrane Proteins, Molecular Sequence Data, Oxidation-Reduction, Phenotype, Polymorphism, Genetic, X Chromosome, Conserved Sequence, Czech Republic, Slovakia, ATP-Binding Cassette Transporters, Palmitic Acid, 5' Untranslated Regions, Mutation, Missense, Polymorphism, Single Nucleotide, Amino Acid Motifs
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
