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A new locus for autosomal dominant Charcot-Marie-Tooth disease type 2 (CMT2L) maps to chromosome 12q24

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Abstract

Charcot-Marie-Tooth disease (CMT) is one of the most common inherited neurological disorders with a prevalence estimated at 1/2500. The axonal form of this disorder is referred to as Charcot-Marie-Tooth type 2 disease (CMT2). Recently, a large Chinese family with CMT2 was found in the Hunan and Hubei provinces of China. The known loci for CMT1A, CMT2D, CMT1B (the same locus is also responsible for CMT2I and CMT2J), CMT2A, CMT2E, and CMT2F were excluded in this family by linkage analysis. A genome-wide screening was then carried out, and the results revealed linkage of CMT2 to a locus at chromosome 12q24. Haplotype construction and analyses localized this novel locus to a 6.8-cM interval between microsatellite markers D12S366 and D12S1611. The maximal two-point LOD score of 6.35 and multipoint LOD score of 8.08 for marker D12S76 at a recombination fraction (θ) of 0 strongly supported linkage to this locus. Thus, CMT2 neuropathy in this family represents a novel genetic entity that we have designated as CMT2L.

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Acknowledgements

We thank the participating families for their cooperation throughout this study. This study was co-funded by a grant from the National 863 High-tech Project (2001AA227011, 2002AA711A07) and National Natural Science Foundation of China (grant nos. 39900047 and 30300200). We are also grateful to Vincent Timmerman (University of Antwerp, Belgium) who kindly donated some of the primers for exclusion analysis.

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Authors and Affiliations

  1. National Laboratory of Medical Genetics of China, Central South University, 410078, Changsha, Hunan, People’s Republic of China

    Bei-sha Tang, Kun Xia, Fang Cai, Qian Pan, He-ping Dai & Jia-hui Xia

  2. Department of Neurology, Xiangya Hospital, Central South University, 410008, Changsha, Hunan, People’s Republic of China

    Bei-sha Tang, Wei Luo, Jian-feng Xiao, Hong Jiang, Lu Shen, Jian-guang Tang, Guo-hua Zhao & Qi-dong Yang

  3. Department of Neurology, First Affiliated Hospital, Medical College of Zhejiang University, 310003, Hangzhou, Zhejiang, People’s Republic of China

    Wei Luo

  4. Columbia Genome Center, Columbia University, New York, USA

    Oleg V. Evgrafov

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  1. Bei-sha Tang
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  2. Wei Luo
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  3. Kun Xia
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Correspondence to Bei-sha Tang.

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Tang, Bs., Luo, W., Xia, K. et al. A new locus for autosomal dominant Charcot-Marie-Tooth disease type 2 (CMT2L) maps to chromosome 12q24. Hum Genet 114, 527–533 (2004). https://doi.org/10.1007/s00439-004-1102-1

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