Inheritance of Charcot-Marie-Tooth disease 1A with rare nonrecurrent genomic rearrangement.
Neurogenetics
; 12(1): 51-8, 2011 Feb.
Article
em En
| MEDLINE
| ID: mdl-21193943
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Rearranjo Gênico
/
Doença de Charcot-Marie-Tooth
Limite:
Female
/
Humans
/
Male
País/Região como assunto:
Asia
Idioma:
En
Revista:
Neurogenetics
Assunto da revista:
GENETICA
/
NEUROLOGIA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Coréia do Sul