Molecular genetic testing for fragile X syndrome: laboratory performance on the College of American Pathologists proficiency surveys (2001-2009).

PURPOSE: The College of American Pathologists offers biannual proficiency testing for molecular analysis of fragile X syndrome. The purpose of this study was to analyze laboratory performance on the fragile X proficiency surveys from 2001 to 2009.
METHODS: Individual laboratory responses were analyzed for accuracy of genotype determination (normal, gray zone, premutation, or full mutation) and size analysis of the FMR1 trinucleotide repeat region. The analytical sensitivity and specificity of testing for fragile X were calculated, and laboratory performance for trinucleotide repeat sizing was evaluated.
RESULTS: Overall, laboratories demonstrated analytical sensitivity of 99% and 96% for detection of full mutations associated with fragile X syndrome in males and females, respectively; analytical sensitivity of 98% for detection of premutations; and analytical specificity of 99.9%. Size measurements of the CGG repeat region were acceptable from most laboratories, with an increase in the range of reported sizes observed for larger repeat expansions.
CONCLUSIONS: Molecular genetic testing for fragile X syndrome demonstrated excellent sensitivity and specificity by laboratories participating in the College of American Pathologists (CAP) surveys. Allele sizing demonstrated good performance overall with improved accuracy over the study period. Participation in proficiency testing can aid laboratories in assessing individual performance and need for calibration of assays.