Summary
The adrenoleukodystrophy gene encodes a peroxisomal integral membrane protein (ALDP) consisting of 745 amino acids with a molecular weight of 75 kDa. ALDP expression was studied in fibroblasts from 24 male ALD patients from 17 unrelated ALD kindreds. In four kindreds an identical 2-base-pair deletion was found. We report the absence of ALDP in 12 kindreds carrying nonsense mutations, frame shifts or amino acid substitutions in the carboxy terminus of ALDP, together accounting for 71% of the ALD kindreds. ALDP was present in five kindreds (29%) with amino acid substitutions in the amino terminal half of the protein; in two of these kindreds ALDP was present although at a reduced level. The absence of truncated proteins suggests that the carboxy terminus has a function in the stabilization of ALDP.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Cartier N, Sarde CO, Douar AM, Mosser J, Mandel JL, Aubourgh P (1993) Abnormal messenger RNA expression and a missense mutation in patients with X-linked adrenoleukodystrophy.Hum Mol Genet 2: 1949–1951.
Contreras M, Mosser J, Mandel JL, Aubourg P, Singh I (1994) The protein coded by the adrenoleukodystrophy gene is a peroxisomal integral membrane protein.FEBS Lett 344: 211–215.
Gärtner J, Moser H, Valle D (1992) Mutations in the 70 K peroxisomal membrane protein gene in Zellweger syndrome.Nature Genet 1: 16–23.
Kamijo K, Taketani S, Yokota S, Osumi T, Hashimoto T (1990) The 70-kDa peroxisomal membrane protein is a member of the Mdr (P-glycoprotein)-related ATP-binding protein superfamily.J Biol Chem 265: 4534–4540.
Kemp S, Ligtenberg MJL, van Geel BM, et al (1994) Identification of a two base pair deletion in five unrelated families with adrenoleukodystrophy: a possible hot spot for mutations.Biochem Biophys Res Commun 202: 647–653.
Kemp S, Ligtenberg MJL, van Geel BM, et al (1995) Two intronic mutations in the adrenoleukodystrophy gene.Hum Mutat 6: 272–273.
Ligtenberg MJL, Kemp S, Sarde CO, et al (1995) Spectrum of mutations in the gene encoding the adrenoleukodystrophy protein.Am J Hum Genet 56: 44–50.
Maestri NE, Beaty TH (1992) Predictions of a 2-locus model for disease heterogeneity: application to adrenoleukodystrophy.Am J Med Genet 44: 576–582.
Moser HW, Moser AB, Trojak JE, Supplee SW (1983) Identification of female carriers of adrenoleukodystrophy.J Pediatr 103: 54–59.
Moser HW, Moser AB, Smith KD, et al (1992) Adrenoleukodystrophy: phenotypic variability and implications for therapy.J Inher Metab Dis 15: 645–664.
Moser HW, Smith KD, Moser A (1995) X-linked adrenoleukodystrophy. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds.The Metabolic and Molecular Bases of Inherited Disease New York: McGraw-Hill, 2325–2350.
Mosser J, Douar AM, Sarde CO, et al (1993) Putative X-linked adrenoleukodystrophy gene shares unexpected homology with ABC transporters.Nature 361: 726–730.
Mosser J, Lutz Y, Stoeckel ME, et al (1994) The gene responsible for adrenoleukodystrophy encodes a peroxisomal membrane protein.Hum Mol Genet 2: 265–271.
Sobue G, Ueno-Natsukari I, Okamoto H, et al (1994) Phenotypic heterogeneity of an adult form of adrenoleukodystrophy in monozygotic twins.Ann Neurol 36: 912–915.
Tager JM, ten Harmsen van der Beek WA, Wanders RJA, et al (1985) Peroxisomalβ-oxidation enzyme proteins in the Zellweger syndrome.Biochem Biophys Res Commun 126: 1269–1275.
Valle D, Gärtner J (1993) Penetrating the peroxisome.Nature 361: 682–683.
Wanders RJA, Van Roermund CWT, Van Wijland MJA, et al (1987) Peroxisomal very-long-chain fatty acidβ-oxidation in human skin fibroblasts: activity in Zellweger syndrome and other peroxisomal disorders.Clin Chim Acta 166: 255–263.
Wanders RJA, Denis S, Ruiter JPN, et al (1995) Measurement of peroxisomal fatty acidβ-oxidation in cultured skin fibroblasts.J Inher Metab Dis 18 (supplement 1): 113–124.
Watkins PA, Gould SJ, Smith MA, et al (1995) Altered expression of ALDP in X-linked adrenoleukodystrophy.Am J Hum Genet 57: 292–301.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kemp, S., Mooyer, P.A.W., Bolhuis, P.A. et al. ALDP expression in fibroblasts of patients with X-linked adrenoleukodystrophy. J Inherit Metab Dis 19, 667–674 (1996). https://doi.org/10.1007/BF01799844
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01799844