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Inheritance of Charcot–Marie–Tooth disease 1A with rare nonrecurrent genomic rearrangement

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Abstract

Rare copy number variations by the nonrecurrent rearrangements involving PMP22 have been recently suggested to be associated with CMT1A peripheral neuropathy. As a mechanism of the nonrecurrent rearrangement, replication-based fork stalling template switching (FoSTeS) by microhomology-mediated break-induced replication (MMBIR) has been proposed. We found three Korean CMT1A families with putative nonrecurrent duplication. The duplications were identified by microsatellite typing and applying a CGH microarray. The breakpoint sequences in two families suggested an Alu–Alu-mediated rearrangement with the FoSTeS by the MMBIR, and a two-step rearrangement of the replication-based FoSTeS/MMBIR and meiosis-based recombination. The two-step mechanism has still not been reported. Segregation analysis of 17p12 microsatellite markers and breakpoint junction analysis suggested that the nonrecurrent rearrangements are stably inherited without alteration of junction sequence; however, they may allow some alteration of the genomic contents in duplication across generations by recombination event. It might be the first study on the pedigree analysis of the large CMT1A families with nonrecurrent rearrangements. It seems that the exact mechanism of the nonrecurrent rearrangements in the CMT1A may have a far more complex process than has been expected.

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Acknowledgments

This study was supported by Mid-career Researcher Program through NRF grant funded by the MEST (R01-2008-000-20604-0 and KRF-2008-313-C00750), Republic of Korea.

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Authors and Affiliations

  1. Department of Neurology, School of Medicine, Ewha Womans University, Seoul, South Korea

    Byung-Ok Choi

  2. Institute for Clinical Research, CHA Bundang Medical Center, School of Medicine, CHA University, Seongnam, South Korea

    Nam Keun Kim

  3. Department of Biological Science, Kongju National University, 182 Sinkwan-dong, Kongju, Chungnam, 314-701, South Korea

    Sun Wha Park, Young Se Hyun, Hyeon Jeong Jeon & Ki Wha Chung

  4. DNA Analysis Division, National Forensic Service, Seoul, 158-097, South Korea

    Jung Hee Hwang

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  1. Byung-Ok Choi
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  2. Nam Keun Kim
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  3. Sun Wha Park
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Correspondence to Ki Wha Chung.

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B.-O. Choi and N.K. Kim contributed equally to this work.

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Choi, BO., Kim, N.K., Park, S.W. et al. Inheritance of Charcot–Marie–Tooth disease 1A with rare nonrecurrent genomic rearrangement. Neurogenetics 12, 51–58 (2011). https://doi.org/10.1007/s10048-010-0272-3

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  • DOI: https://doi.org/10.1007/s10048-010-0272-3

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