Mutational analyses on X-linked adrenoleukodystrophy reveal a novel cryptic splicing and three missense mutations in the ABCD1 gene.

[x-linked adrenoleukodystrophy]

X-linked adrenoleukodystrophy is caused by a defective peroxisomal membrane transporter , ABCD 1 , responsible for transporting very -long -chain fatty acid substrate into peroxisomes for degradation . The main biochemical defect , which is also one of the major diagnostic hallmarks , of X-linked adrenoleukodystrophy is the accumulation of saturated very -long -chain fatty acids in all tissues and body fluids .Direct and reverse-transcribed polymerase chain reactions followed by DNA sequencing-based mutational analyses were performed on one Taiwanese and three Malaysian X-linked adrenoleukodystrophy families .A novel splicing donor site mutation (c .1272 +1 g >a ) was identified in a Taiwanese X-linked adrenoleukodystrophy patient , resulting in a deletion of 121 Â bp and a premature stop codon (p .Val 425 fs *92 ) in messenger-RNA transcript . This deletion is caused by the activation of a cryptic splicing donor site in exon 4 of the ABCD 1 gene , which is consistent with the prediction by several online algorithms . In addition , three previously described missense mutations (c .965 T >C , c .1978 C >T , and c .2006 A >G ), leading to aberrant ABCD 1 of p .Leu 322 Pro , p .Arg 660 Trp , and p .His 669 Arg , were also identified in Malaysian probands .This is the first report to unveil unequivocally that cryptic splicing-induced aberrant messenger-RNA carrying an internal frameshift deletion results from an intronic mutation in the ABCD 1 gene . Furthermore , a polymorphism in intron 9 (c .1992 -32 c /t ; refSNP : rs 4898368 ) of the ABCD 1 gene was commonly observed in both Taiwanese and Malaysian populations .

Diseases
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Diseases presenting "previously described missense mutations" symptom

x-linked adrenoleukodystrophy

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