ABCD1 mutations and the X-linked adrenoleukodystrophy mutation database: Role in diagnosis and clinical correlations
ABCD1 mutations and the X-linked adrenoleukodystrophy mutation database: Role in diagnosis and clinical correlations
复制标题
DOI：
10.1002/humu.1227
复制
发表时间：
2001-01-01
期刊：
影响因子：
3.9
通讯作者：
Hugo, HW
中科院分区：
文献类型：
--
作者：
Kemp, S;Pujol, A;Hugo, HW
X连锁肾上腺脑白质营养不良（X-ALD）是由ABCD 1基因突变引起的，该基因编码过氧化物酶体ABC半转运蛋白（ALDP），参与极长链脂肪酸（VLCFA）进入过氧化物酶体。该疾病的特征在于表型表达的显著和不可预测的变化。表型包括快速进展的儿童期脑型（CCALD）、较温和的成人型、肾上腺脊髓神经病（AMN）和无神经系统受累的变体。基因型与表型之间无明显相关性。在男性中，可以通过证明血浆中VLCFA水平升高来实现明确的诊断。然而，在15%到20%的专性杂合子中，检测结果是假阴性的。因此，突变分析是鉴定杂合子的唯一可靠方法。由于大多数X-ALD激酶具有独特的突变，在过去的七年中，ABCD 1基因中已经发现了大量的突变。为了对这些突变进行分类和便于分析，我们建立了X-ALD的突变数据库（http：www.x-ald.nl）。在这篇综述中，我们报告了数据库中目前包含的所有406个X-ALD突变的详细分析。此外，我们提出了47个新的突变。此外，我们回顾了各种X-ALD表型，不同的诊断工具，以及需要大家庭筛查新患者的识别。2001年，《突变》18：499-515。(C)2001 Wiley-Liss，Inc.
X-linked adrenoleukodystrophy (X-ALD) is caused by mutations in the ABCD1 gene, which encodes a peroxisomal ABC half-transporter (ALDP) involved in the import of very long-chain fatty acids (VLCFA) into the peroxisome. The disease is characterized by a striking and unpredictable variation in phenotypic expression. Phenotypes include the rapidly progressive childhood cerebral form (CCALD), the milder adult form, adrenomyeloneuropathy (AMN), and variants without neurologic involvement. There is no apparent correlation between genotype and phenotype. In males, unambiguous diagnosis can be achieved by demonstration of elevated levels of VLCFA in plasma. In 15 to 20% of obligate heterozygotes, however, test results are false-negative. Therefore, mutation analysis is the only reliable method for the identification of heterozygotes. Since most X-ALD kindreds have a unique mutation, a great number of mutations have been identified in the ABCD1 gene in the last seven years. In order to catalog and facilitate the analysis of these mutations, we have established a mutation database for X-ALD (http://www.x-ald.nl). In this review we report a detailed analysis of all 406 X-ALD mutations currently included in the database. Also, we present 47 novel mutations. In addition, we review the various X-ALD phenotypes, the different diagnostic tools, and the need for extended family screening for the identification of new patients. Hum Mutat 18:499-515, 2001. (C) 2001 Wiley-Liss, Inc.