title: Inheritance of Charcot-Marie-Tooth disease 1A with rare nonrecurrent genomic rearrangement.
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.
authors.affiliation: Department of Neurology, School of Medicine, Ewha Womans University, Seoul, South Korea.
authors.forename: Byung-Ok
authors.initials: BO
authors.lastname: Choi
authors.forename: Nam Keun
authors.initials: NK
authors.lastname: Kim
authors.forename: Sun Wha
authors.initials: SW
authors.lastname: Park
authors.forename: Young Se
authors.initials: YS
authors.lastname: Hyun
authors.forename: Hyeon Jeong
authors.initials: HJ
authors.lastname: Jeon
authors.forename: Jung Hee
authors.initials: JH
authors.lastname: Hwang
authors.forename: Ki Wha
authors.initials: KW
authors.lastname: Chung
mesh_terms: D020087:Alu Elements; D001483:Base Sequence; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D004247:DNA / Q000235:genetics; D056915:DNA Copy Number Variations; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D008297:Male; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D056910:Republic of Korea
chemical_list: D004247:DNA