S149R, a novel mutation in the ABCD1 gene causing X-linked adrenoleukodystrophy
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Fang Yan1,*, Wenbo Wang2,3,4,*, Hui Ying2,3,4, Hongyu Li5, Jing Chen6 and Chao Xu2,3,4
1Department of Pain Management, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, China
2Department of Endocrinology and Metabolism, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, China
3Institute of Endocrinology, Shandong Academy of Clinical Medicine, Jinan, Shandong 250021, China
4Shandong Clinical Medical Center of Endocrinology and Metabolism, Jinan, Shandong 250021, China
5Department of Pain Management, Ankang City People’s Hospital, Ankang, Shanxi 725000, China
6Department of Child Health, Xiamen Maternal and Child Health Hospital, Xiamen, Fujian 361003, China
*These authors have contributed equally to this work
Chao Xu, email: [email protected]
Keywords: X-linked adrenoleukodystrophy, ABCD1 gene, peroxisomal disorder, genetic diagnosis, bioinformatics analysis
Received: March 31, 2017 Accepted: August 26, 2017 Published: September 18, 2017
X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder. It is a heterogeneous disorder caused by mutations in the ATP-binding cassette protein subfamily D1 (ABCD1) gene, encoding the peroxisomal membrane protein ALDP, which is involved in the transmembrane transport of very long-chain fatty acids. For the first time, we report a case of olivopontocerebellar X-ALD on the Chinese mainland. In this study, a novel mutation (c.447T>A; p.S149R) in ABCD1 was detected in a patient diagnosed with X-ALD. The mutant amino acid is well conserved among species. Bioinformatics analysis predicted the substitution to be deleterious and to cause structural changes in the adrenoleukodystrophy protein. Immunofluorescence showed an altered subcellular localization of the S149R mutant protein, which may lead to defects in the degradation of very long chain fatty acids in peroxisomes. We therefore suggest that the novel mutation, which alters ALDP structure, subcellular distribution and function, is responsible for X-ALD.
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