Identification of a new complementation group of the peroxisome biogenesis disorders and PEX14 as the mutated gene
Identification of a new complementation group of the peroxisome biogenesis disorders and PEX14 as the mutated gene
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DOI：
10.1002/humu.20032
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发表时间：
2004-06-01
期刊：
影响因子：
3.9
通讯作者：
Kondo, N
中科院分区：
文献类型：
--
作者：
Shimozawa, N;Tsukamoto, T;Kondo, N
过氧化物酶体生物发生障碍（PBD）是由过氧化物酶体生物发生异常引起的致命遗传性疾病。目前，已鉴定出 12 个不同的互补组，并且迄今为止，负责每个互补组的所有基因均已被鉴定。过氧化物酶体膜蛋白 PEX14 是过氧化物酶体输入机制的关键组成部分，可能是两个输入受体 PEX5 和 PEX7 的初始对接位点。尽管 PEX14 突变体已在酵母和 CHO 细胞中被发现，但人类 PEX14 缺陷显然尚未有记录。我们现在报道了以 PEx14 作为缺陷基因的过氧化物酶体生物发生障碍的新互补组的鉴定。事实上，人类 PEX14 挽救了属于新互补组的 Zellweger 综合征患者的成纤维细胞过氧化物酶体中 PTS1 依赖性和 PTS2 依赖性蛋白质的导入。该患者在 PEX14 的推定卷曲螺旋区域 c.553C>T (p.Q185X) 中具有无义突变纯合子。此外，我们通过免疫细胞化学分析发现，患者的成纤维细胞缺乏 PEX14。这些发现表明 PBD 中有 13 种基因型，PEX14 的作用在人类中也至关重要。 (C) 2004 Wiley-Liss, Inc.
Peroxisome biogenesis disorders (PBD) are lethal hereditary diseases caused by abnormalities in the biogenesis of peroxisomes. At present, 12 different complementation groups have been identified and to date, all genes responsible for each of these complementation groups have been identified. The peroxisomal membrane protein PEX14 is a key component of the peroxisomal import machinery and may be the initial docking site for the two import receptors PEX5 and PEX7. Although PEX14 mutants have been identified in yeasts and CHO-cells, human PEX14 deficiency has apparently not been documented. We now report the identification of a new complementation group of the peroxisome biogenesis disorders with PEx14 as the defective gene. Indeed, human PEX14 rescues the import of a PTS1-dependent as well as a PTS2-dependent protein into the peroxisomes in fibroblasts from a patient with Zellweger syndrome belonging to the new complementation group. This patient was homozygous for a nonsense mutation in a putative coiled-coil region of PEX14, c.553C>T (p.Q185X). Furthermore, we showed that the patient's fibroblasts lacked PEX14 as determined by immunocytochemical analysis. These findings indicate that there are 13 genotypes in PBD and that the role of PEX14 is also essential in humans. (C) 2004 Wiley-Liss, Inc.