Ignite Creation Date:
2024-05-05 @ 5:33 PM
Last Modification Date:
2024-10-26 @ 9:33 AM
Study NCT ID:
NCT00474331
Status:
SUSPENDED
Last Update Posted:
2022-05-18
First Post:
2007-05-14
Brief Title:
Gene Mutations and Orthopaedic Symptoms Correlation of Multiple Hereditary Exostoses Multicentre Project
Sponsor:
University of British Columbia
Organization:
University of British Columbia
Study Overview
Official Title:
Genotype-Phenotype Correlation of Multiple Hereditary Exostoses Multicentre Project
Status:
SUSPENDED
Status Verified Date:
2017-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Due to unavailability of testing for gene mutation
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The investigators goal for this project is to examine the causes of the wide variability of the expression of Hereditary Multiple Exostoses HME Previous work completed by our group shows that there exists a correlation between genotype and phenotype such that certain mutations or affected genes cause certain patterns of presentation symptoms and signs The investigators intend to achieve this goal by increasing our study sample size to build upon the results generated from the pilot project of this study in order to obtain statistical significance This will be achieved by performing genotype-phenotype analysis on new families presenting with HME in British Columbia
Detailed Description:
Subject Recruitment
New patients presenting with HME will be identified through the offices and clinics of British Columbia Childrens Hospital Orthopaedic Department All potential participants will be educated about the studys rationale purpose and procedures and informed consent will be obtained
Demographics
All probands affected patient their first degree family members and extended family members willing to participate in the study will be interviewed Information including age gender ethnic origin family history symptoms complications and previous surgery will be elucidated
Phenotype
Affected patients will have their osteochondromas mapped for location size morphology and symptoms A total of seventy-five phenotypic parameters divided into four major data categories will be collected The first two categories are accumulated from physical examinations and include stature and limb segment lengths 15 x2 for left and right The other two categories lesion quality 19 parameters and limb alignment and deformity 26 parameters will be drawn from radiographic examinations which are part of the patients current care All available xrays will be reviewed and the exostoses characterized radiographically This will establish the patients genotype
Genotype
Each participant whose genotype is unknown will have a 10 cc blood sample collected at BC Childrens Hospital This sample will be processed for mutation analysis DNA extraction from blood samples mutation analysis at the Clinical Molecular Diagnostic Laboratory at BC Childrens Hospital The techniques used in the pilot study will be implemented with the exception that microsatellite markers will not be used in order to save cost
Using EXT 1 and EXT 2 primers Appendix 1 both strands of a DNA segment are sequenced using ABI Big Dye chemistry Version 2 The resulting sequencing reaction products are then run on an ABI 3100 Avant genetic analyzer Once a sequence is obtained it is analyzed with SeqScape version 2 software which allows comparison with reference sequence
Data Analysis
All information resulting from this research study will be kept strictly confidential All documents will be identified by an ID number and kept in locked filing cabinets Participants will not be identified by name in any reports of the completed study Databases will be stored on project-dedicated laptop computer which is locked in the research office
The phenotypic data collected will be used to describe family degrees designed using Cyrillic software phenotypes of affected individuals and mutations in the exostoses genes of interest site and type of mutation Subject heights and segment lengths will be converted to percentile figures to standardize for age and gender to allow for comparison amongst groups
Genotypic data from the mutation analysis of blood samples will include location of the mutation early in the gene versus late in the gene type of mutation alteration of gene as missense frameshift nonsense or splice site and the amino acid change that was caused by the mutation The data will be analyzed as follows
Preliminary Analysis
1 EXT 1 versus EXT 2
2 Males versus Females
3 EXT 1 males versus EXT 1 females versus EXT 2 males versus EXT 2 females
Secondary Analysis
4 Types of mutations Missense versus Nonsense versus Splice site versus Frameshift
5 Early or late mutation less than 1700 base pairs versus greater than 1700 base pairs
With 2-way analyses an unpaired t-test will be calculated and with greater than 2-way analyses an ANOVA will be calculated Power will be calculated for every comparison due to the huge variation in sample size Statistical significance will be set to prior at 005 and power of 08
New patients presenting with HME will be identified through the offices and clinics of British Columbia Childrens Hospital Orthopaedic Department All potential participants will be educated about the studys rationale purpose and procedures and informed consent will be obtained
Demographics
All probands affected patient their first degree family members and extended family members willing to participate in the study will be interviewed Information including age gender ethnic origin family history symptoms complications and previous surgery will be elucidated
Phenotype
Affected patients will have their osteochondromas mapped for location size morphology and symptoms A total of seventy-five phenotypic parameters divided into four major data categories will be collected The first two categories are accumulated from physical examinations and include stature and limb segment lengths 15 x2 for left and right The other two categories lesion quality 19 parameters and limb alignment and deformity 26 parameters will be drawn from radiographic examinations which are part of the patients current care All available xrays will be reviewed and the exostoses characterized radiographically This will establish the patients genotype
Genotype
Each participant whose genotype is unknown will have a 10 cc blood sample collected at BC Childrens Hospital This sample will be processed for mutation analysis DNA extraction from blood samples mutation analysis at the Clinical Molecular Diagnostic Laboratory at BC Childrens Hospital The techniques used in the pilot study will be implemented with the exception that microsatellite markers will not be used in order to save cost
Using EXT 1 and EXT 2 primers Appendix 1 both strands of a DNA segment are sequenced using ABI Big Dye chemistry Version 2 The resulting sequencing reaction products are then run on an ABI 3100 Avant genetic analyzer Once a sequence is obtained it is analyzed with SeqScape version 2 software which allows comparison with reference sequence
Data Analysis
All information resulting from this research study will be kept strictly confidential All documents will be identified by an ID number and kept in locked filing cabinets Participants will not be identified by name in any reports of the completed study Databases will be stored on project-dedicated laptop computer which is locked in the research office
The phenotypic data collected will be used to describe family degrees designed using Cyrillic software phenotypes of affected individuals and mutations in the exostoses genes of interest site and type of mutation Subject heights and segment lengths will be converted to percentile figures to standardize for age and gender to allow for comparison amongst groups
Genotypic data from the mutation analysis of blood samples will include location of the mutation early in the gene versus late in the gene type of mutation alteration of gene as missense frameshift nonsense or splice site and the amino acid change that was caused by the mutation The data will be analyzed as follows
Preliminary Analysis
1 EXT 1 versus EXT 2
2 Males versus Females
3 EXT 1 males versus EXT 1 females versus EXT 2 males versus EXT 2 females
Secondary Analysis
4 Types of mutations Missense versus Nonsense versus Splice site versus Frameshift
5 Early or late mutation less than 1700 base pairs versus greater than 1700 base pairs
With 2-way analyses an unpaired t-test will be calculated and with greater than 2-way analyses an ANOVA will be calculated Power will be calculated for every comparison due to the huge variation in sample size Statistical significance will be set to prior at 005 and power of 08
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None