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首页> 外文期刊>Journal of neurology >Copy number variations are a rare cause of non-CMT1A Charcot-Marie-Tooth disease.
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Copy number variations are a rare cause of non-CMT1A Charcot-Marie-Tooth disease.

机译：拷贝数变异是引起非CMT1A夏科-玛丽齿病的罕见原因。

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摘要

Hereditary peripheral neuropathies present a group of clinically and genetically heterogeneous entities. All known forms, including the various forms of Charcot-Marie-Tooth disease (CMT) are characterized as Mendelian traits and over 35 genes have been identified thus far. The mutational mechanism of the most common CMT type, CMT1A, is a 1.5 Mb chromosomal duplication at 17p12 that contains the gene PMP22. Only recently it has been realized that such copy number variants (CNV) are a widespread phenomenon and important for disease. However, it is not known whether CNVs play a wider role in hereditary peripheral neuropathies outside of CMT1A. In a phenotypically heterogeneous sample of 97 patients, we performed the first high-density CNV study of 34 genomic regions harboring known genes for hereditary peripheral neuropathies including the 17p12 duplication region, with comparative genomic hybridization (CGH) microarrays. We identified three CNVs that affected coding exons. A novel shorter form of a PMP22 duplication was detected in a CMT1A family previously tested negative in a commercial test. Two other CNVs in MTMR2 and ARHGEF10 are likely not disease associated. Our results indicate that CNVs are a rare cause for non-CMT1A CMT. Their potential relevance as disease modifiers remains to be evaluated. The present study design cannot rule out that specific CMT forms exist where CNVs play a larger role.
机译：遗传性周围神经病表现出一组临床和遗传异质实体。所有已知形式，包括各种形式的夏科-玛丽-牙齿疾病（CMT），都被表征为孟德尔性状，迄今为止已鉴定出35种以上的基因。最常见的CMT类型CMT1A的突变机制是在17p12处包含基因PMP22的1.5 Mb染色体重复。直到最近才意识到，这样的拷贝数变体（CNV）是一种普遍的现象并且对疾病很重要。但是，尚不清楚CNV是否在CMT1A之外的遗传性周围神经病中发挥更广泛的作用。在97位患者的表型异质性样本中，我们使用比较基因组杂交（CGH）微阵列技术对34个基因组区域进行了首次高密度CNV研究，这些基因组区域包含遗传性外周神经病的已知基因，包括17p12复制区域。我们确定了三个影响编码外显子的CNV。在先前在商业测试中测试为阴性的CMT1A系列中检测到了新型的PMP22重复形式的较短形式。 MTMR2和ARHGEF10中的另外两个CNV可能与疾病无关。我们的结果表明，CNV是非CMT1A CMT的罕见原因。它们作为疾病改良剂的潜在相关性尚待评估。本研究设计不能排除CNV发挥更大作用的特定CMT形式。

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