Copy number variations are a rare cause of non-CMT1A Charcot-Marie-Tooth disease.
Copy number variations are a rare cause of non-CMT1A Charcot-Marie-Tooth disease.
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DOI：
10.1007/s00415-009-5401-2
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发表时间：
2010-05
影响因子：
6
通讯作者：
Züchner S
中科院分区：
文献类型：
--
作者：
Huang J;Wu X;Montenegro G;Price J;Wang G;Vance JM;Shy ME;Züchner S
遗传性周围神经病呈现一组临床和遗传异质性实体。所有已知的形式，包括各种形式的腓骨肌萎缩症（CMT）的特征是孟德尔性状和超过35个基因已被确定至今。最常见的CMT类型CMT1A的突变机制是在17p12处的1.5 Mb染色体重复，其包含基因PMP 22。直到最近才认识到，这种拷贝数变异（CNV）是一种普遍现象，对疾病很重要。然而，目前尚不清楚CNV是否在CMT1A以外的遗传性周围神经病变中发挥更广泛的作用。在97例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周围神经病的已知基因，包括17p12重复区域。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检测为阴性的CMT1A家族中检测到一种新的较短形式的PMP 22重复。MTMR 2和ARHGEF 10中的另外两个CNV可能与疾病无关。我们的研究结果表明，CNVs是非CMT1A CMT的罕见原因。它们作为疾病调节剂的潜在相关性仍有待评估。本研究设计不能排除特定CMT形式存在的CNVs发挥更大的作用。
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.
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影响因子：
30.8
作者：
Xu, Bin;Roos, J. Louw;Karayiorgou, Maria
通讯作者：
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Walsh, Christopher A.
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Iafrate, AJ;Feuk, L;Lee, C
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Lee, C
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作者：
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Wigler, M
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Stone, Jennifer L.;O'Donovan, Michael C.;Gurling, Hugh;Kirov, George K.;Blackwood, Douglas H. R.;Corvin, Aiden;Craddock, Nick J.;Gill, Michael;Hultman, Christina M.;Lichtenstein, Paul;McQuillin, Andrew;Pato, Carlos N.;Ruderfer, Douglas M.;Owen, Michael J.;St Clair, David;Sullivan, Patrick F.;Sklar, Pamela;Purcell, Shaun M.;Scolnick, E. M.;Holmans, P. A.;Georgieva, L.;Nikolov, I.;Norton, N.;Williams, H.;Williams, N. M.;Toncheva, D.;Milanova, V.;Thelander, E. F.;Morris, D. W.;O'Dushlaine, C. T.;Kenny, E.;Waddington, J. L.;Choudhury, K.;Datta, S.;Pimm, J.;Thirumalai, S.;Puri, V.;Krasucki, R.;Lawrence, J.;Quested, D.;Bass, N.;Curtis, D.;Crombie, C.;Fraser, G.;Kwan, S. L.;Muir, W. J.;McGhee, K. A.;Pickard, B.;Malloy, P.;Maclean, A. W.;Van Beck, M.;Visscher, P. M.;Macgregor, S.;Pato, M. T.;Medeiros, H.;Middleton, F.;Carvalho, C.;Morley, C.;Fanous, A.;Conti, D.;Knowles, J. A.;Ferreira, C. P.;Azevedo, M. H.;McCarroll, S. A.;Gates, C.;Daly, M. J.;Sklar, P.
通讯作者：
Sklar, P.