Evidence against the Adrenoleukodystrophy-related Gene acting as a Modifier of X-adrenoleukodystrophy

Abstract

Mutations in the ALD gene encoding a peroxisomal ABC-transporter are the cause of X-linked adrenoleukodystrophy (X-ALD). The clinical course of the disease is extremely heterogeneous, ranging from severe phenotypes leading to death in early childhood to asymptomatic forms. Mutation analysis in X-ALD patients showed no predictable genotype-phenotype correlation. Out of 3 peroxisomal ABC-transporters the human adrenoleukodystrophy related protein (hALDRP, Holzinger et al. 1997) displays the highest homology to the adrenoleukodystrophy protein (ALDP). ALDRP can restore P-oxidation in X-ALD fibroblasts in in vitro expression experiments and directly interacts with ALDP.