Consensus characterization of 16 FMR1 reference materials: a consortium study
Jean Amos Wilson1, Victoria M Pratt, Amit Phansalkar
1Sequenom, San Diego, California, USA.
The Journal of Molecular Diagnostics : JMD
|January 1, 2008
Summary
Characterized DNA reference materials for Fragile X syndrome testing are now available. These materials aid in accurate diagnosis and quality control for the Fragile X mental retardation 1 (FMR1) gene assay.
Area of Science:
- Genetics
- Molecular Biology
- Clinical Diagnostics
Background:
- Fragile X syndrome, caused by FMR1 gene (CGG)n repeat expansion, leads to intellectual disability.
- FMR1 premutations are linked to premature ovarian failure and fragile X-associated tremor/ataxia syndrome.
- FMR1 gene analysis is challenging due to high GC content and PCR limitations.
Purpose of the Study:
- To address the need for reliable reference materials for FMR1 gene analysis.
- To develop and validate characterized DNA samples for Fragile X mutation testing.
- To improve the accuracy and quality control of clinical Fragile X syndrome diagnostics.
Main Methods:
- Development of characterized DNA samples from 16 cell lines with diverse FMR1 (CGG)n repeat lengths.
- Consensus analysis of FMR1 alleles by nine independent clinical laboratories.
- Characterization of DNA samples representing key phenotypic classes and diagnostic cutoffs.
Main Results:
- Creation of a set of 16 characterized DNA reference materials for FMR1 gene analysis.
- Consensus data from nine labs validated the repeat lengths and phenotypic associations.
- Availability of these reference materials through the Coriell Cell Repositories.
Conclusions:
- Publicly available, characterized FMR1 reference materials are crucial for accurate Fragile X syndrome testing.
- These materials will support test development, validation, and routine quality control.
- Enhanced diagnostic accuracy for Fragile X syndrome and related disorders is anticipated.
