identification of new polymorphism in the adrenoleukodystrophy gene permits genetic testing of the disease in the UAE

ABSTRACT

X-linked adrenoleukodystrophy [ALD] affects 1/20,000 males either as cerebral ALD in childhood or as adrenomyeloneuropathy in adults. ALD, the most frequent peroxisomal disorder is a severe neurodegenerative disease associated with an impairment of very long chain fatty acid - oxidation. The recent characterization of the ALD gene [this gene is 21 kilobase pairs long and it encodes a 745 amino acid protein] will permit the identification of mutations in ALD patients, which will allow diagnosis of the disease by genetic testing. To that end, we have designed a pilot project that allowed us to screen 5 of the 10 exons of the ALD gene, using a strategy based upon the technique of denaturing gradient gel electrophoresis coupled to asymmetric amplication DNA sequencing. We have identified the first polymorphism of the ALD gene; it is due to a G-to-A silent mutation in codon 506 [leucine] of the gene [corresponding to nucleotide 1934] and is therefore designated L506L. This polymorphism allowed us to follow the cosegregation of the disease allele in the family of an affected boy of Pakistani origin who had been referred to Tawam Hospital. Moreover, the frequency of L506L is 15% in the U.A.E. population; this polymorphism will therefore be useful for genetic counselling in the country