Determination of the mutation spectrum of the EXT1/EXT2 genes in British Caucasian patients with multiple osteochondromas, and exclusion of six candidate genes in EXT negative cases.
We describe here the spectrum and distribution of mutations in the EXT1 and EXT2 genes in the largest reported British Caucasian multiple osteochondromas (MO) population. Furthermore, we report for the first time the screening of the EXT1 and EXT2 promoters, 5'UTRs, and 3'UTRs, and exclude six potential MO candidate genes in individuals without a detectable mutation within the coding region of EXT1 and EXT2. The coding exons of EXT1 and EXT2 were screened in 72 unrelated probands affected with MO. Forty-six different mutations were identified in 56 probands, of which 29 were novel. Mutation in the EXT1 and EXT2 genes each accounted for 50% of the mutations identified. Of the 72 probands, 42 were of British Caucasian descent, which when added to the 41 British Caucasian families previously reported from our total cohort, gave a total of 83 families. This cohort's proportional frequency for EXT1/EXT2 mutation was 53%/47%. We also validated the technique of high-resolution melting analysis in a blind study using 27 unique EXT1 or EXT2 mutations. This technique was found to be sensitive with a detection rate of 100% regarding heterozygote detection for EXT mutation scanning. Furthermore, this technique has a very high throughput and is very cost-effective.
Lonie
Lorne
L
The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom. lorne@well.ox.ac.uk
Porter
Daniel E
DE
Fraser
Maria
M
Cole
Trevor
T
Wise
Carol
C
Yates
Laura
L
Wakeling
Emma
E
Blair
Ed
E
Morava
Eva
E
Monaco
Anthony P
AP
Ragoussis
Jiannis
J
D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005091:Exons; D005097:Exostoses, Multiple Hereditary / Q000235:genetics*; D005820:Genetic Testing / Q000379:methods; D015894:Genome, Human; D006801:Humans; D009154:Mutation; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics*; D016366:Open Reading Frames / Q000235:genetics; D011401:Promoter Regions, Genetic; D012107:Research Design; D044366:Transition Temperature; D006113:United Kingdom; D044465:White People / Q000235:genetics; D000099065:Exostosin 2; D000099058:Exostosin 1
D017351:N-Acetylglucosaminyltransferases; D000099058:Exostosin 1; D000099065:Exostosin 2