S149R, a novel mutation in the ABCD1 gene causing X-linked adrenoleukodystrophy.
S149R, a novel mutation in the ABCD1 gene causing X-linked adrenoleukodystrophy.
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S149R，ABCD1 基因中的一种新突变，导致 X 连锁肾上腺脑白质营养不良
DOI：
10.18632/oncotarget.20974
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发表时间：
2017-10-20
期刊：
影响因子：
--
通讯作者：
Xu C
中科院分区：
文献类型：
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作者：
Yan F;Wang W;Ying H;Li H;Chen J;Xu C
X连锁肾上腺脑白质营养不良（X-ALD）是最常见的过氧化物酶体疾病。它是一种异质性疾病，由ATP结合盒蛋白亚家族D1（ABCD 1）基因突变引起，编码过氧化物酶体膜蛋白ALDP，参与极长链脂肪酸的跨膜转运。本文报告一例发生于中国大陆的橄榄桥脑小脑型酒精性肝病。在这项研究中，在诊断为X-ALD的患者中检测到ABCD 1的新突变（c.447T>A; p.S149R）。突变氨基酸在物种间是很保守的。生物信息学分析预测取代是有害的，并导致肾上腺脑白质营养不良蛋白的结构变化。免疫荧光显示S149 R突变蛋白的亚细胞定位改变，这可能导致过氧化物酶体中非常长链脂肪酸降解的缺陷。因此，我们认为，新的突变，改变ALDP的结构，亚细胞分布和功能，是负责X-ALD。
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.