Ca. Wise et al., IDENTIFICATION AND LOCALIZATION OF THE GENE FOR EXTL, A 3RD MEMBER OFTHE MULTIPLE EXOSTOSES GENE FAMILY, PCR methods and applications, 7(1), 1997, pp. 10-16
Hereditary multiple exostoses (EXT) is an autosomal dominant disorder
characterized by multiple bony outgrowths From the juxtaepiphyseal reg
ion of long bones. In a small proportion of cases, these exostoses pro
gress to malignant chondrosarcomas. Genetic linkage of this disorder h
as been described to three independent loci on chromosomes 8q24.1 (EXT
1), 11p11-13 (EXT2), and 19p (EXT-3). The EXT1 and EXT2 genes were iso
lated recently and show extensive sequence homology to each other. The
se genes are deleted in exostoses-derived tumors, supporting the hypot
hesis that they encode tumor suppressors. We have identified a third g
ene that shows striking sequence similarity to both EXT1 and EXT2 at t
he nucleotide and amino acid sequence levels, and have derived its ent
ire coding sequence. Although the mRNA transcribed from this gene is s
imilar in size to that from EXT1 and EXT2, its pattern of expression i
s quite different. We have localized this gene by fluorescence in situ
hybridization to metaphase chromosomes and by whole genome radiation
hybrid mapping to chromosome 1p36.1 between D15458 and DIS511, a regio
n that frequently shows loss of heterozygosity in a variety of tumor t
ypes. This gene, EXTL (for EXT-like), is therefore a new member of the
EXT gene family and is a potential candidate for several disease phen
otypes.