title: Mutation screening of EXT1 and EXT2 by direct sequence analysis and MLPA in patients with multiple osteochondromas: splice site mutations and exonic deletions account for more than half of the mutations.
abstract: Multiple osteochondromas (MO) is an autosomal dominant condition, caused by mutations in either the EXT1 or the EXT2 gene. The DNA of a cohort of 35 patients, clinically suspected to be affected with MO, was screened for mutations by a combination of direct sequence analysis and multiplex ligation-dependent probe amplification (MLPA). In this cohort, 26 pathogenic gene alterations were found (74%). With sequence analysis mutations were detected in 22 patients (63%). In total, 10 mutations were detected in the EXT1 and 12 in the EXT2 gene. The number of the splice site mutations detected was larger than expected from the literature. In addition, with the MLPA four deletions of one or more exons were found in this cohort. Two patients, of whom one had a negative family history, showed deletions of exon 1 of the EXT1 gene, which is possibly a deletion hot spot. In patients suspected to be affected by MO, we recommend a quantitative analysis such as MLPA, followed by direct sequence analysis for the screening of the EXT1 and EXT2 genes.
authors.affiliation: Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands. g.r.vink@lumc.nl
authors.forename: Geraldine R
authors.initials: GR
authors.lastname: Vink
authors.forename: Stefan J
authors.initials: SJ
authors.lastname: White
authors.forename: Strelicija
authors.initials: S
authors.lastname: Gabelic
authors.forename: Pancras C W
authors.initials: PC
authors.lastname: Hogendoorn
authors.forename: Martijn H
authors.initials: MH
authors.lastname: Breuning
authors.forename: Egbert
authors.initials: E
authors.lastname: Bakker
mesh_terms: D015331:Cohort Studies; D005091:Exons / Q000235:genetics*; D005097:Exostoses, Multiple Hereditary / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D009154:Mutation / Q000235:genetics*; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012326:RNA Splicing / Q000235:genetics*; D017421:Sequence Analysis; D017384:Sequence Deletion; D000099065:Exostosin 2; D000099058:Exostosin 1
chemical_list: D017351:N-Acetylglucosaminyltransferases; D000099058:Exostosin 1; D000099065:Exostosin 2