Zellweger Syndrome Caused by PEX13 Deficiency: Report of Two Novel Mutations
Zellweger Syndrome Caused by PEX13 Deficiency: Report of Two Novel Mutations
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DOI：
10.1002/ajmg.a.32874
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发表时间：
2009-06-01
影响因子：
2
通讯作者：
Alkuraya, F. S.
中科院分区：
文献类型：
--
作者：
Al-Dirbashi, O. Y.;Shaheen, R.;Alkuraya, F. S.
过氧化物酶体生物发生障碍是一组遗传异质性的疾病，它们具有过氧化物酶体正常组装的共同失败。临床表现为畸形、神经系统、肝脏和其他器官受累。迄今为止，编码过氧化物酶的13个PEX基因突变已在过氧化物酶体生物发生障碍患者中被发现。编码过氧化物酶体膜蛋白PEX13的PEX13突变是过氧化物酶体生物发生障碍最不常见的原因之一，迄今为止仅报道了三种突变。在这里，我们报告了两个婴儿，他们的临床和生化特征与经典的齐薇格综合征一致，他们的互补分析将他们都分配到过氧化物酶体生物发生障碍的H组。我们发现它们在PEX13中有两个新的突变。一名患者的基因组重排导致整个PEX13缺失147 kb，而另一名患者则出现了14 bp的框外缺失。这是关于PEX13缺失的第一份报告，表明需要进一步研究阿拉伯过氧化物酶体生物发生障碍患者中PEX13突变的频率。(C) 2009 Wiley-Liss, Inc。
Peroxisomal biogenesis disorders represent a group of genetically heterogeneous conditions that have in common failure of proper peroxisomal assembly. Clinically, they are characterized by a spectrum of dysmorphia, neurological, liver, and other organ involvement. To date, mutations in 13 PEX genes encoding peroxins have been identified in patients with peroxisomal biogenesis disorders. Mutations in PEX13, which encodes peroxisomal membrane protein PEX13, are among the least common causes of peroxisomal biogenesis disorders with only three mutations reported so far. Here, we report on two infants whose clinical and biochemical profile was consistent with classical Zellweger syndrome and whose complementation analysis assigned them both to group H of peroxisomal biogenesis disorders. We show that they harbor two novel mutations in PEX13. One patient had a genomic rearrangement resulting in a 147 kb deletion that spans the whole of PEX13, while the other had an out-of-frame deletion of 14 bp. This represents the first report of a PEX13 deletion and suggests that further work is needed to examine the frequency of PEX13 mutations among Arab patients with peroxisomal biogenesis disorders. (C) 2009 Wiley-Liss, Inc.