X-ALD is a neurological disorder associated with inherited defects in the ABCD1 (ALD) gene located on Xq28 and with impaired peroxisomal very long-chain fatty acid beta-oxidation. We examined the ABCD1 gene in probands from 11 unrelated X-ALD Czech and Slovak families by the direct sequencing of cDNA or genomic PCR products. In 10 families there were 10 different mutations, eight of which were novel. The spectrum of mutations consists of six point mutations, three microdeletions (1bp, 2bp, 4 bp), and one large deletion (229bp). In the 11th family we detected two novel single-base pair substitutions in exon 1 (c.38 A>C and c.649 A>G), both causing amino acid exchanges (N13T and K217E). Expression studies revealed that only K217E is a deleterious mutation, because a plasmid encoding ALDP with K217E was ineffective in the restoration of defective beta-oxidation in X-ALD fibroblasts. The N13T amino acid exchange, on the other hand, did not affect ALDP function. Thus, N13T represents the first polymorphism causing an amino acid exchange in the ABCD1 gene. As this polymorphism was observed neither in 100 control alleles nor in 300 X-ALD patients who have been sequenced so far world-wide, it seems to be very rare or unique. Two additional novel polymorphisms were found by the sequencing of the ABCD1 gene from our patients: c.-59 C/T in the 5'untranslated region and c.2019 C/T (F673F) in exon 10. The frequencies of these two polymorphisms, were 11/150 and 2/150 control alleles, respectively.

• MeSH
• 5' Untranslated Regions genetics   MeSH
• ATP Binding Cassette Transporter, Subfamily D, Member 1 MeSH
• ATP-Binding Cassette Transporters chemistry   genetics   MeSH
• Adrenoleukodystrophy genetics   MeSH
• Alleles MeSH
• Amino Acid Motifs MeSH
• X Chromosome genetics   MeSH
• Child MeSH
• Adult MeSH
• Exons genetics   MeSH
• Phenotype MeSH
• Genetic Linkage genetics   MeSH
• Polymorphism, Single Nucleotide genetics   MeSH
• Conserved Sequence MeSH
• Palmitic Acid metabolism   MeSH
• Humans MeSH
• Fatty Acids metabolism   MeSH
• Membrane Proteins chemistry   genetics   MeSH
• Mutation, Missense genetics   MeSH
• Adolescent MeSH
• Molecular Sequence Data MeSH
• DNA Mutational Analysis MeSH
• Oxidation-Reduction MeSH
• Polymorphism, Genetic genetics   MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Czech Republic MeSH
• Slovakia MeSH
• Names of Substances
• 5' Untranslated Regions MeSH
• ATP Binding Cassette Transporter, Subfamily D, Member 1 MeSH
• ATP-Binding Cassette Transporters MeSH
• ABCD1 protein, human MeSH Browser
• Palmitic Acid MeSH
• lignoceric acid MeSH Browser
• Fatty Acids MeSH
• Membrane Proteins MeSH