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Ainhi D. Ha, MBBS 1 , Christopher A. Beck, PhD 2 , Joseph Jankovic, MD 1

Intermediate CAG repeats: Analysis of the Cooperative Huntington’s Observational Research Trial (COHORT). Ainhi D. Ha, MBBS 1 , Christopher A. Beck, PhD 2 , Joseph Jankovic, MD 1

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Ainhi D. Ha, MBBS 1 , Christopher A. Beck, PhD 2 , Joseph Jankovic, MD 1

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  1. Intermediate CAG repeats: Analysis of the Cooperative Huntington’s Observational Research Trial (COHORT) Ainhi D. Ha, MBBS1, Christopher A. Beck, PhD2, Joseph Jankovic, MD1 1Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, Texas 2Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, New York No Relevant Financial Disclosures

  2. The American College of Medical Genetics/American Society of Human Genetics (ACMG/ASHG) Huntington Disease Genetic Testing Working Group

  3. Can Intermediate Repeats Cause Clinical Manifestations of Huntington’s Disease? 1Kenney et al (2007), 2Squitieri et al (2011), 3Andrich et al (2008), 4Herishanu et al (2009), 5Groen et al (2010),

  4. Aim • To define the clinical characteristics of individuals who possess intermediate length CAG repeats in the Huntingtin (HTT) gene.

  5. Methods • Analysis of COHORT • 1985 subjects • HD (CAG >=36): 1290 (65%) • Intermediate (CAG 27-35): 50 (2.5%) • Normal (CAG <=26): 645 (32%) • Investigators blinded to CAG repeat length • Baseline data

  6. Distribution of Subjects with Intermediate CAG Repeats (N=50)

  7. Unified Huntington’s Disease Rating Scale (UHDRS) • Motor • Oculomotor function • Dysarthria • Chorea • Dystonia • Gait • Postural stability • Cognitive • Verbal Fluency • Symbol Digit Modalities • Stroop Interference Test • Behavioral • Depressed mood • Apathy • Suicidal thoughts • Anxiety • Delusions • Hallucinations • Functional • Independence scale • Functional capacity • Functional assessment

  8. UHDRS: Motor Domain Comparisons Mean (SD)

  9. UHDRS: Behavioral Domain Comparisons Mean (SD)

  10. UHDRS: Cognitive Domain Comparisons Mean (SD)

  11. Comparison of Individual UHDRS Motor Items between Normal and Intermediate Groups

  12. Comparison of Individual UHDRS Behavioral Items between Normal and Intermediate Groups

  13. Comparison of Intermediate Vs Normal and HD

  14. Summary: Intermediate vs. normal • Comparison of Means: • Total Maximal Dystonia Score (p=0.001) • UHDRS Stroop word reading (p=0.019) • Comparison of Distributions Across Individual UHDRS Scores: • Motor • Vertical Saccade Velocity (p=0.045) • Maximal Dystonia RUE (p= 0.004) • Maximal Chorea LLE (p=0.026) • Behavior • Depressed Mood – Severity (p=0.019) • Suicidal Thoughts Severity (p= 0.013) • History of at least one suicide attempt (p=0.049)

  15. Conclusions • Differences in UHDRS scores were identified between normal and intermediate groups on exploratory analysis. • The presence of intermediate CAG repeats may influence the phenotype of these individuals.

  16. Acknowledgements • Huntington Study Group • Dr. Ray Dorsey • Dr. Ira Shoulson • Anthony Davidson • Statistical analysis conducted by Dr. Christopher A. Beck

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