Identification of an unusual variant peroxisome biogenesis disorder caused by mutations in the PEX16 gene
Identification of an unusual variant peroxisome biogenesis disorder caused by mutations in the PEX16 gene
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DOI：
10.1136/jmg.2009.074302
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发表时间：
2010-09-01
影响因子：
4
通讯作者：
Ferdinandusse, Sacha
中科院分区：
文献类型：
--
作者：
Ebberink, Mere S.;Csanyi, Barbara;Ferdinandusse, Sacha
背景齐薇格综合征谱系障碍是由至少12种不同PEX基因中的任何一种突变引起的。这包括PEX16，其编码参与过氧化物酶体膜组装的完整过氧化物酶体膜蛋白。据报道，PEX16缺陷患者具有严重的临床表现。从这些患者的成纤维细胞表现出一个缺陷的进口过氧化物酶体基质和膜蛋白，导致在一个总的情况下的过氧化物酶体residuals.ObjectiveTo报告6例患者的一个意想不到的轻度变异过氧化物酶体生物合成障碍，由于在PEX16基因突变。患者在学龄前表现为进行性痉挛性下肢轻瘫和共济失调（MRI扫描显示特征性进行性脑白质营养不良和脑萎缩），后来发展为白内障和周围神经病变。令人惊讶的是，他们的成纤维细胞表现出扩大，进口主管peroxisomes.Results血浆分析显示生化异常提示过氧化物酶体紊乱。成纤维细胞中的生化变量仅轻度异常或在正常范围内。免疫荧光显微镜显示存在进口主管过氧化物酶体，这是增加的大小，但数量减少。所有已知的PEX基因的后续测序发现五个新的明显的纯合突变的PEX16 gene.Conclusions一个不寻常的变体过氧化物酶体生物合成障碍所造成的突变的PEX16基因，一个相对温和的临床表型和一个意想不到的表型成纤维细胞，被确定。虽然PEX16参与过氧化物酶体膜组装，但PEX16缺陷可在成纤维细胞中存在扩大的进口能力过氧化物酶体。这对于将来诊断患有过氧化物酶体障碍的患者是重要的。
Background Zellweger syndrome spectrum disorders are caused by mutations in any of at least 12 different PEX genes. This includes PEX16, which encodes an integral peroxisomal membrane protein involved in peroxisomal membrane assembly. PEX16-defective patients have been reported to have a severe clinical presentation. Fibroblasts from these patients displayed a defect in the import of peroxisomal matrix and membrane proteins, resulting in a total absence of peroxisomal remnants.Objective To report on six patients with an unexpected mild variant peroxisome biogenesis disorder due to mutations in the PEX16 gene. Patients presented in the preschool years with progressive spastic paraparesis and ataxia (with a characteristic pattern of progressive leucodystrophy and brain atrophy on MRI scan) and later developed cataracts and peripheral neuropathy. Surprisingly, their fibroblasts showed enlarged, import-competent peroxisomes.Results Plasma analysis revealed biochemical abnormalities suggesting a peroxisomal disorder. Biochemical variables in fibroblasts were only mildly abnormal or within the normal range. Immunofluorescence microscopy revealed the presence of import-competent peroxisomes, which were increased in size but reduced in number. Subsequent sequencing of all known PEX genes revealed five novel apparent homozygous mutations in the PEX16 gene.Conclusions An unusual variant peroxisome biogenesis disorder caused by mutations in the PEX16 gene, with a relatively mild clinical phenotype and an unexpected phenotype in fibroblasts, was identified. Although PEX16 is involved in peroxisomal membrane assembly, PEX16 defects can present with enlarged import-competent peroxisomes in fibroblasts. This is important for future diagnostics of patients with a peroxisomal disorder.