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
この論文をさがす
説明
We diagnosed an adrenomyeloneuropathy (AMN) patient with a double novel missense mutation, c.284CA (p.A95D) and c.290AT (p.H97L) in a single ABCD1 allele. In skin fibroblasts from the patient, no ABCD1 protein was detected by immunoblot analysis, and the C24:0 β-oxidation activity was decreased to a level at which the ABCD1 protein was absent. To determine the responsible gene mutation in the patient, we constructed three kinds of mutated ABCD1 gene expression vectors (c.284CA, c.290AT or c.284CA/c.290AT) and transfected them into CHO cells stably expressing GFP-SKL (CHO/GFP-SKL cells) or CADDS fibroblasts lacking the ABCD1 gene. ABCD1 (p.H97L) displayed the correct peroxisomal localization in CHO/GFP-SKL cells, but ABCD1 (p.A95D) and ABCD1 (p.A95D/p.H97L) were diffuse in the cytosol. Furthermore, ABCD1 (p.H97L) was detected by immunoblot analysis and restored the C24:0 β-oxidation activity in the CADDS fibroblasts, as the wild type ABCD1 did. On the other hand, ABCD1 (p.A95D) and ABCD1 (p.A95D/p.H97L) were not detected and the C24:0 β-oxidation activity was not restored. These results clearly show that c.284CA is the responsible gene mutation, whereas c.290AT is a novel polymorphism.
収録刊行物
-
- JIMD Reports
-
JIMD Reports 10 95-102, 2012
Springer Berlin Heidelberg
