Identification of new mutations in Israeli patients with X-linked adrenoleukodystrophy

X-linked adrenoleukodystrophy (ALD) is a peroxisomal disorder characterized by impaired peroxisomal beta -oxidation of very-long-chain fatty acids (VL CFAs), This is probably due to reduced activation of the VLCFAs and results in demyelination of the nervous system and adrenocortical insufficiency. T he ALD gene is localized on Xq28, has 10 exons and encodes a protein of 745 amino acids with significant homology to the membrane peroxisomal protein PMP70, Characterizing the disease causing mutations is of importance in pre natal diagnosis because 12-20% of women who are obligatory carriers show fa lse-negative results when tested for VLCFA in plasma. We have analyzed DNA from blood samples of 7 Jewish (5 Sephardi and 2 Ashkenazi) and 3 Arab Isra eli families suffering from ALD. Five missense-type mutations were identifi ed: R104H, Y174C, L229P, R401Q, and G512C, A single mutation, R464X, was no nsense, and two, Y171 frameshift and E471 frameshift, were frameshift, Inte restingly, a single mutation was identified in three families of Moroccan J ewish descent, probably due to a founder effect.