ALDP expression in fibroblasts of patients with X-linked adrenoleukodystrophy

• Published in: Journal of inherited metabolic disease Vol. 19; no. 5; p. 667
• Main Authors: Kemp, S, Mooyer, P A, Bolhuis, P A, van Geel, B M, Mandel, J L, Barth, P G, Aubourg, P, Wanders, R J
• Format: Journal Article
• Language: English
• Published: United States 01.01.1996
• Subjects: Adrenoleukodystrophy - genetics; Adrenoleukodystrophy - metabolism; ATP Binding Cassette Transporter, Subfamily D, Member 1; ATP-Binding Cassette Transporters - genetics; ATP-Binding Cassette Transporters - metabolism; Cell Line; Fibroblasts - metabolism; Frameshift Mutation; Gene Expression; Genetic Linkage; Humans; Male; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mutation; Phenotype; Point Mutation; Sequence Deletion; X Chromosome
• ISSN: 0141-8955
• DOI: 10.1007/BF01799844

The adrenoleukodystrophy gene encodes a peroxisomal integral membrane protein (ALDP) consisting of 745 amino acids with a molecular weight of 75kDa. 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.