Molecular genetics of adrenoleukodystrophy
- Kennedy Krieger Institute, Baltimore, MD (United States); and others
Adrenoleukodystrophy (ALD) is an X-linked disorder characterized by deficient peroxisomal metabolism of very long chain fatty acids (VLCFA) and reduced activity of CLCFA-CoA ligase. The most frequent clinical manifestation of ALD is a generalized and rapidly progressive demyelination of the brain associated with perivascular inflammation. A putative gene for ALD (ALDP) was recently isolated that surprisingly codes for a protein that belongs to a family of transmembrane transporters regulated or activated by ATP. It appears to be half-transporter with a coding sequence of 2238 base pairs (bp). We have assayed for mutations in the putative ALDP gene in ALD patients. We detected large deletions in the carboxyl-terminal portion of the gene in 4 of 100 patients. Twenty-six patients with intact ALDP genes were surveyed for mutations by Single Strand Conformation Polymorphism (SSCP) procedures. SSCP variants were detected in 19, while 7 were normal for all ALDP exons and its promoter region. No variants were found in 28 ALDP genes from normal individuals. Mutations within the variant SSCP fragments were determined by DNA sequence analysis. The mutations were distributed throughout the gene; most were missense mutation except for an unusual cluster of small insertions and deletions in the 96 bp exon 5. An identical AG deletion within exon 5 was found in 7 unrelated patients. These data strongly support the notion that mutations in the putative ALD gene result in ALD. The possibility of a second X-linked gene for ALD is suggested by the failure to detect mutations in a significant fraction of the patients examined.
- OSTI ID:
- 133430
- Report Number(s):
- CONF-941009--
- Journal Information:
- American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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