IDENTIFICATION OF MUTATIONS IN THE ALD-GENE OF 20 FAMILIES WITH ADRENOLEUKODYSTROPHY ADRENOMYELONEUROPATHY

Adrenoleukodystrophy (ALD), an X-linked inherited metabolic disorder, is the most frequent inborn peroxisomal disease. It leads to demyelina tion in the central and peripheral nervous system. Defective beta-oxid ation of saturated very long chain fatty acids (VLCFAs; C22:0-C26:0) i n peroxisomes has been shown to lead to an accumulation of VLCFAs in l eukoid areas of the central nervous system, peripheral nerves, adrenal land, and blood. The ALD gene has been recently identified and encode s a 745-amino-acid protein. We screened patients with adrenoleukodystr ophy/adrenomyeloneuropathy (ALD/AMN) from 20 kindreds for mutations in the ALD gene. Eleven missense and two nonsense mutations. five deleti ons, and one insertion were detected by direct sequencing of eight rev erse transcribed fragments of the ALD-gene mRNA. Four mutations could be shown to be de novo. All mutations could be confirmed in carriers b y sequencing genomic DNA. No correlation between the type of mutation and the severity of the phenotype could be observed. The mutations wer e not detected in the ALD gene of 30 healthy persons.