Premium
Intronic deletion and duplication proximal of the EXT1 gene: A novel causative mechanism for multiple osteochondromas
Author(s) -
Waaijer Cathelijn J. F.,
Winter Marcel G. T.,
Reijnders Christianne M. A.,
de Jong Daniëlle,
John Ham S.,
Bovée Judith V. M. G.,
Szuhai Károly
Publication year - 2013
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.22041
Subject(s) - breakpoint , gene duplication , genetics , biology , intron , gene , locus (genetics) , germline , chromosomal translocation
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. © 2013 Wiley Periodicals, Inc.