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. 2020 Aug 20;10(9):575.
doi: 10.3390/brainsci10090575.

The Association between CAG Repeat Length and Age of Onset of Juvenile-Onset Huntington's Disease

Jordan L Schultz  1   2 , Amelia D Moser  3 , Peg C Nopoulos  1   2   4
Affiliations

The Association between CAG Repeat Length and Age of Onset of Juvenile-Onset Huntington's Disease

Jordan L Schultz et al. Brain Sci. .

Abstract

There is a known negative association between cytosine-adenine-guanine (CAG) repeat length and the age of motor onset (AMO) in adult-onset Huntington's Disease (AOHD). This relationship is less clear in patients with juvenile-onset Huntington's disease (JOHD), however, given the rarity of this patient population. The aim of this study was to investigate this relationship amongst a relatively large group of patients with JOHD using data from the Kids-JOHD study. Additionally, we analyzed data from the Enroll-HD platform and the Predict-HD study to compare the relationship between CAG repeat length and AMO amongst patients with AOHD to that amongst patients with JOHD using linear regression models. In line with previous reports, the variance in AMO that was predicted by CAG repeat length was 59% (p < 0.0001) in the Predict-HD study and 57% from the Enroll-HD platform (p < 0.0001). However, CAG repeat length predicted 84% of the variance in AMO amongst participants from the Kids-JOHD study (p < 0.0001). These results indicate that there may be a stronger relationship between CAG repeat length and AMO in patients with JOHD as compared to patients with AOHD. These results provide additional information that may help to model disease progression of JOHD, which is beneficial for the planning and implementation of future clinical trials.

Keywords: CAG; juvenile-onset Huntington’s disease; motor onset.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Mean scores on the various domains of the Unified Huntington’s Disease Rating Scale (UHDRS). Specifically, ocular pursuit score is the mean of horizontal and vertical pursuit scores; saccade initiation is the mean of the horizontal and vertical initiation scores; saccade velocity is the mean of the horizontal and vertical velocity scores; finger tapping is the mean of the right and left hand scores; pronate/supinate is the mean of the right and left hand scores; rigidity is the mean of the scores in the right and left arms; dystonia score is the mean scores from the trunk, right and left upper extremities, and right and left lower extremities; chorea score is the mean of maximal chorea scores from the face, buccal-oral-lingual scores, trunk, right and left upper extremities, and right and left lower extremities. All other scores include only one component and represent the mean of that domain.
Figure 2
Figure 2
Cytosine–adenine–guanine (CAG) repeat length significantly predicts the age of motor onset in (A) patients with juvenile-onset Huntington’s disease (JOHD) from the Kids-JOHD study, (B) patients with adult-onset Huntington’s Disease (AOHD) from the Predict-HD study, and (C) patients with AOHD from the Enroll-HD study. Black lines show the predicted regression lines, and the gray ribbons display the 95% confidence intervals.
See this image and copyright information in PMC

References

    1. Macdonald M.E., Ambrose C.M., Duyao M.P., Myers R.H., Lin C., Srinidhi L., Barnes G., Taylor S.A., James M., Groot N., et al. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. Cell. 1993;72:971–983. doi: 10.1016/0092-8674(93)90585-E. - DOI - PubMed
    1. Langbehn D.R., Brinkman R., Falush D., Paulsen J.S., Hayden M.R. A new model for prediction of the age of onset and penetrance for Huntington’s disease based on CAG length. Clin. Genet. 2004;65:267–277. doi: 10.1111/j.1399-0004.2004.00241.x. - DOI - PubMed
    1. Stine O., Pleasant N., Franz M.L., Abbott M.H., Folstein S.E., Ross C.A. Correlation between the onset age of Huntington’s disease and length of the trinucleotide repeat in IT-15. Hum. Mol. Genet. 1993;2:1547–1549. doi: 10.1093/hmg/2.10.1547. - DOI - PubMed
    1. Lucotte G., Turpin J., Riess O., Epplen J.T., Siedlaczk I., Loirat F., Hazout S. Confidence intervals for predicted age of onset, given the size of (CAG) n repeat, in Huntington’s disease. Qual. Life Res. 1995;95:231–232. doi: 10.1007/BF00209410. - DOI - PubMed
    1. Andrew S.E., Goldberg Y.P., Kremer B., Telenius H., Theilmann J., Adam S., Starr E., Squitieri F., Lin B., Kalchman M.A., et al. The relationship between trinucleotide (CAG) repeat length and clinical features of Huntington’s disease. Nat. Genet. 1993;4:398–403. doi: 10.1038/ng0893-398. - DOI - PubMed

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