1. ¹Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
2. ²Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands

Correspondence: Dr GR Vink, Center for Human and Clinical Genetics, Leiden University Medical Center, Wassenaarseweg 72, 2333AL Leiden, The Netherlands. Tel: +31 71 527 6082; Fax: +31 71 527 1601; E-mail: g.r.vink@lumc.nl

Received 29 July 2004; Revised 21 October 2004; Accepted 22 October 2004; Published online 8 December 2004.

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.