Assessing the analytic validity of molecular testing for Huntington disease using data from an external proficiency testing survey

Glenn E. Palomaki, Carolyn (Sue) Richards

Research output: Contribution to journalArticle

19 Scopus citations


Purpose: Documenting high analytic validity of the molecular diagnostic test for Huntington disease is important because of counseling implications. This dominantly inherited adult onset disorder (prevalence of three or more per 100,000) is characterized by chorea, ataxia, and personality changes. The molecular basis is excessive CAG repeats in the HTT gene. Methods: External proficiency testing survey results for Huntington disease were extracted (2003-2010). Analytic interpretations and CAG repeat lengths were compared with published performance criteria. Results: Between 2008 and 2010, 33 US participating laboratories reported clinical test interpretations. Analytic validity was high (sensitivity: 99.5%, 95% confidence interval: 97.1-99.9%; specificity: 99.2%, 95% confidence interval: 97.1-99.9%). Repeat length errors occurred in 2.6% (95% confidence interval: 1.8-3.8%) of 1,060 allelic challenges, with most being minor or from a single participant. Past performance (2003-2007) was similar. The 23 international participants had more total repeat length errors (17.5%, 95% confidence interval: 14.6-20.7%). Further analyses indicated that assessment criteria can be relaxed without jeopardizing analytic validity. Conclusion: Analytic validity is high for Huntington disease testing among US laboratories. International survey participants had lower analytic validity and a higher proportion of poorly performing laboratories. The reasons for this are unclear.

Original languageEnglish (US)
Pages (from-to)69-75
Number of pages7
JournalGenetics in Medicine
Issue number1
StatePublished - 2012



  • analytic validity
  • external proficiency testing
  • Huntington disease
  • quality assurance

ASJC Scopus subject areas

  • Genetics(clinical)

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