A Novel Double Mutation in the ABCD1 Gene in a Patient with X-linked Adrenoleukodystrophy: Analysis of the Stability and Function of the Mutant ABCD1 Protein.

[adrenomyeloneuropathy]

We diagnosed an adrenomyeloneuropathy (AMN ) patient with a double novel missense mutation , c .284 C >A (p .A 95 D ) and c .290 A >T (p .H 97 L ) in a single ABCD 1 allele . In skin fibroblasts from the patient , no ABCD 1 protein was detected by immunoblot analysis , and the C 2 4 :0 Î²-oxidation activity was decreased to a level at which the ABCD 1 protein was absent . To determine the responsible gene mutation in the patient , we constructed three kinds of mutated ABCD 1 gene expression vectors (c .284 C >A , c .290 A >T or c .284 C >A /c .290 A >T ) and transfected them into CHO cells stably expressing GFP-SKL (CHO /GFP-SKL cells ) or CADDS fibroblasts lacking the ABCD 1 gene . ABCD 1 (p .H 97 L ) displayed the correct peroxisomal localization in CHO /GFP-SKL cells , but ABCD 1 (p .A 95 D ) and ABCD 1 (p .A 95 D /p .H 97 L ) were diffuse in the cytosol . Furthermore , ABCD 1 (p .H 97 L ) was detected by immunoblot analysis and restored the C 2 4 :0 Î²-oxidation activity in the CADDS fibroblasts , as the wild type ABCD 1 did . On the other hand , ABCD 1 (p .A 95 D ) and ABCD 1 (p .A 95 D /p .H 97 L ) were not detected and the C 2 4 :0 Î²-oxidation activity was not restored . These results clearly show that c .284 C >A is the responsible gene mutation , whereas c .290 A >T is a novel polymorphism .

Diseases
Validation

Diseases presenting "double novel missense mutation" symptom

adrenomyeloneuropathy

x-linked adrenoleukodystrophy

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