Mutational analyses of Taiwanese kindred with X-linked adrenoleukodystrophy.
X-linked adrenoleukodystrophy is a neurodegenerative disorder with highly variable clinical presentation, including the childhood cerebral form, adult form adrenomyeloneuropathy, and Addison disease. The biochemical hallmark of the disorder is the accumulation of saturated very long chain fatty acids in all tissues and body fluids. This accumulation results from mutations in the ABCD1 gene localized to Xq28. Using polymerase chain reaction and direct sequencing of deoxyribonucleic acid, we identified five novel mutations, including a microdeletion (1624 del ATC), a splicing site mutation (intervening sequence 1 [IVS1] -2a>c), and three missense mutations (1172 T>C, 1520 G>A, and 1754 T>C), from Taiwanese kindred with X-linked adrenoleukodystrophy. A polymorphism involving a single nucleotide deletion in the intervening sequence 5 (IVS5 -6 del c) of the ABCD1 gene, previously misattributed as a mutation in the Chinese population, was also identified. The dinucleotide deletion (1415 del AG) mutation common in Japan and Western countries was not found as frequently in the Chinese and Taiwanese populations. Instead, a higher mutation frequency was observed in exon 6 of the ABCD1 gene among Japanese, Chinese, and Taiwanese kindred with X-linked adrenoleukodystrophy, representing a potential mutational hotspot for future mutational screening among these Asian populations.
Chiu
Hou-Chang
HC
School of Medicine, Fu Jen Catholic University, Department of Neurology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, Republic of China.
Liang
Jao-Shwann
JS
Wang
Jinn-Shyan
JS
Lu
Jyh-Feng
JF
D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000326:Adrenoleukodystrophy / Q000208:ethnology / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D002648:Child; D002872:Chromosome Deletion; D041321:Chromosomes, Human, X; D003431:Cross-Cultural Comparison; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D020125:Mutation, Missense / Q000235:genetics; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics; D017422:Sequence Analysis, DNA; D013624:Taiwan
C115572:ABCD1 protein, human; D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters