Genotype-phenotype correlations in hereditary multiple exostoses in British Columbia
department or school: Surgery, Department of
department or school: Medicine, Faculty of
data provider: DSpace
degree campus: UBCV
creator: Alvarez, Christine M.
issued: 2009-10-19T22:05:31Z
issued: 2003
related degree: Master of Science - MSc
degree grantor: University of British Columbia
description: Hereditary Multiple Exostosis is an autosomal dominant condition in which multiple benign cartilage-capped tumours grow in relation to the growth plates of long and flat bones. HME has a wide spectrum of clinical presentations and results in considerable morbidity from lesions due to mass effect causing limb deformity, mal-alignment, and shortening. Mutations in EXT 1 and 2 genes result in multiple exostoses. The presumptive role of the EXT genes is either tumour suppression or growth plate regulation. The purpose of this study was to determine the relationship between the genotype and phenotype in HME. Ten families were identified with HME. Genotyping was completed by linkage analysis of all families and the EXT 1 or 2 gene was sequenced based on these results. Mutation identification and confirmation was performed. Phenotyping consisting of clinical and radiographic examinations generated 89 features for each subject. Thirty-two affected individuals from 10 families participated. Eight of 10 mutations were identified, confirmed and segregation verified. Six of the mutations were unique and 2 previously had been reported in the literature. Three mutations were in EXT 1 and 5 in EXT 2. Two were missense, 3 nonsense, 2 splice site and 1 frameshift. EXT 1 patients were found to have more exostoses, with a higher percentage of flat and pelvic bone involvement. EXT 1 patients had more mal-alignment and were shorter. Males also had a more severe phenotype and modulated the severity of EXT 1 expression. No other genotypic factors were found to influence phenotype. An established genotype phenotype correlation will aid in patient management in terms of surveillance, determining prognosis and mangement. In conclusion a genotype phenotype correlation exists where EXT 1 is linked to a more severe phenotype.
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/14060
extent: 11159477 bytes
format: application/pdf
note: ^ Genotype-Phenotype Correlations in Hereditary Multiple Exostoses in British Columbia By Christine M . Alvarez B.Sc, University of Victoria, 1986 M.D., University of British Columbia, 1993 FRCSC, Royal College of Physicians and Surgeons of Canada, 1998 A THESIS SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE In THE FACULTY OF GRADUATE STUDIES (Faculty of Medicine, Department of Surgery) We accept this thesis as conforming to the required standard THE UNIVERSITY OF BRITISH COLUMBIA April 2003 © Christine M. Alvarez, 2003 In presenting this thesis in partial fulfilment of the requirements for an advanced degree at the University of British Columbia, I agree that the Library shall make it freely available for reference and study. I further agree that permission for extensive copying of this thesis for scholarly purposes may be granted by the head of my department or by his or her representatives. It is understood that copying or publication of this thesis for financial gain shall not be allowed without my written permission. Department of The University of British Columbia Vancouver, Canada Date DE-6 (2/88) Abstract Hereditary Multiple Exostosis is an autosomal dominant condition in which multiple benign cartilage-capped tumours grow in relation to the growth plates of long and flat bones. . HME has a wide spectrum of clinical presentations and results in considerable morbidity from lesions due to mass effect causing limb deformity, mal-alignment, and shortening. Mutations in EXT 1 and 2 genes result in multiple exostoses. The presumptive role of the EXT genes is either tumour suppression or growth plate regulation. The purpose of this study was to determine the relationship between the genotype and phenotype in HME. Ten families were identified with HME. Genotyping was completed by linkage analysis of all families and the EXT 1 or 2 gene was sequenced based on these results. Mutation identification and confirmation was performe…
has type: Thesis/Dissertation
date issued: 2003-05
is shown at: 10.14288/1.0090919
language: eng
degree discipline: Surgery
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.
scholar level: Graduate
type: Text
identifier URI: http://hdl.handle.net/2429/14060