title: Identification of a nonsense mutation in ALD protein cDNA from a patient with adrenoleukodystrophy.
abstract: The molecular basis of X-linked adrenoleukodystrophy (ALD) was investigated. Six (A to 50) fragments of cDNA for ALD protein (Mosser et al. Nature 361: 726-730, 1993) from an adult patient with adrenomyeloneuropathy were amplified by PCR and mutations were screened by Mutation Detection Enhancement gel electrophoresis. A single base substitution (2154 C-->T, which resulted in the formation of a termination codon for glutamine (Q590STOP) and deletes Pst I site (CTGCAG-->CTGTAG), was detected. Eight other ALD patients did not have this mutation. A family study revealed the presence of both the mutant and normal alleles in the mother, a sister and a niece, indicating that these individuals were carriers. A nephew with childhood ALD who died 10 years earlier had the same mutant allele as detected by Pst I restriction assay. This report is the first description of a mutant allele for ALD, at the cDNA level, and presents confirmatory evidence of ALD protein as the primary etiology of ALD.
authors.affiliation: Department of Pediatrics, Gifu University School of Medicine, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Uchiyama
authors.forename: Y
authors.initials: Y
authors.lastname: Suzuki
authors.forename: X Q
authors.initials: XQ
authors.lastname: Song
authors.forename: T
authors.initials: T
authors.lastname: Fukao
authors.forename: A
authors.initials: A
authors.lastname: Imamura
authors.forename: S
authors.initials: S
authors.lastname: Tomatsu
authors.forename: N
authors.initials: N
authors.lastname: Shimozawa
authors.forename: N
authors.initials: N
authors.lastname: Kondo
authors.forename: T
authors.initials: T
authors.lastname: Orii
mesh_terms: D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters; D000326:Adrenoleukodystrophy / Q000235:genetics*; D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D018076:DNA, Complementary / Q000235:genetics*; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D005091:Exons / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D005973:Glutamine / Q000235:genetics; D006801:Humans; D007564:Japan; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009692:Nucleic Acid Heteroduplexes / Q000235:genetics; D010375:Pedigree; D017354:Point Mutation; D017384:Sequence Deletion; D013728:Terminator Regions, Genetic / Q000235:genetics; D014960:X Chromosome
chemical_list: C115572:ABCD1 protein, human; D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters; D002352:Carrier Proteins; D018076:DNA, Complementary; D008565:Membrane Proteins; D009692:Nucleic Acid Heteroduplexes; D005973:Glutamine; C024388:CTGCAG-specific type II deoxyribonucleases; D015252:Deoxyribonucleases, Type II Site-Specific