Whole Genome Sequencing Identifies a 78 kb Insertion from Chromosome 8 as the Cause of Charcot-Marie-Tooth Neuropathy CMTX3

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Next generation sequencing technologies have greatly advanced disease gene discovery for Charcot-Marie-Tooth (CMT) disease and related inherited peripheral neuropathies. However, many families with CMT remain unsolved after all protein-coding sequences have been interrogated through whole exome sequencing. The pathogenic mutations in these unsolved families may be non-coding point mutations, small indels or large structural variations involving thousands to millions of base pairs. In two large, distantly related families with X-linked CMT, all known protein-coding sequence variants were tested and no causal variant was found. Using whole genome sequencing we identified a 78 kb 8q24.3 insertion at chromosome Xq27.1 as the likely underlying cause of neuropathy in these two families. This is the first report of a large insertion causing CMT and highlights an understudied disease mechanism for inherited peripheral neuropathy.

Vyšlo v časopise: Whole Genome Sequencing Identifies a 78 kb Insertion from Chromosome 8 as the Cause of Charcot-Marie-Tooth Neuropathy CMTX3. PLoS Genet 12(7): e32767. doi:10.1371/journal.pgen.1006177
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1006177

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