Intronic deletion and duplication proximal of the EXT1 gene: a novel causative mechanism for multiple osteochondromas.

Multiple osteochondromas (MO) is a syndrome in which benign cartilage-capped neoplasms develop at the surface of the long bones. Most cases are caused by exonic changes in EXT1 or EXT2, but 15% are negative for these changes. Here we report for the first time a family of MO patients with germline genomic alterations at the EXT1 locus without detectable mutations or copy number alterations of EXT exonic sequences. Array-CGH showed an 80.7 kb deletion of Intron 1 of EXT1 and a 68.9 kb duplication proximal of EXT1. We identified a breakpoint between the distal end of the duplicated region and a sequence distal of the deleted region in the first intron. This breakpoint was absent in non-affected family members. The configuration of the breakpoint indicates a direct insertion of the duplicated region into the deletion. However, no other breakpoint was found, which suggests a more complex genomic rearrangement has occurred within the duplicated region. Our results reveal intronic deletion and duplication as a new causative mechanism for MO not detected by conventional diagnostic methods. Copyright © 2013 Wiley Periodicals, Inc.

Citation

Cathelijn J F Waaijer, Marcel G T Winter, Christianne M A Reijnders, Daniëlle de Jong, S John Ham, Judith V M G Bovée, Károly Szuhai. Intronic deletion and duplication proximal of the EXT1 gene: a novel causative mechanism for multiple osteochondromas. Genes, chromosomes & cancer. 2013 Apr;52(4):431-6

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PMID: 23341036

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