A Huntington’s Disease (HD) Phenocopy Leads to the Identification of the HD Toxin as Polyalanine. The Relationship between Repeat Length and Age of Onset can be reframed as a Rate Equation and the Toxic Polyalanine Length is found to be About 30.6

2021 ◽  
Vol 02 (02) ◽  
Author(s):  
Tarnow E
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Rate Equation ◽  
Age Of Onset ◽  
Repeat Length ◽  
The Relationship

scholarly journals The Association between CAG Repeat Length and Age of Onset of Juvenile-Onset Huntington’s Disease

2020 ◽  
Vol 10 (9) ◽  
pp. 575 ◽  
Author(s):  
Jordan L. Schultz ◽  
Amelia D. Moser ◽  
Peg C. Nopoulos
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Age Of Onset ◽  
Repeat Length ◽  
Cag Repeat ◽  
Linear Regression Models ◽  
Juvenile Onset ◽  
Additional Information ◽  
Using Data ◽  
The Relationship

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.

The Relationship Between CAG Repeat Length and Age of Onset Differs for Huntington's Disease Patients with Juvenile Onset or Adult Onset

2006 ◽  
Vol 71 (3) ◽  
pp. 295-301 ◽  
Author(s):  
J. Michael Andresen ◽  
Javier Gayán ◽  
Luc Djoussé ◽  
Simone Roberts ◽  
Denise Brocklebank ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Age Of Onset ◽  
Repeat Length ◽  
Cag Repeat ◽  
Adult Onset ◽  
Juvenile Onset ◽  
The Relationship

The relationship between CAG repeat length and clinical progression in Huntington's disease

2008 ◽  
Vol 23 (9) ◽  
pp. 1223-1227 ◽  
Author(s):  
Bernard Ravina ◽  
Megan Romer ◽  
Radu Constantinescu ◽  
Kevin Biglan ◽  
Alicia Brocht ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Repeat Length ◽  
Cag Repeat ◽  
Clinical Progression ◽  
The Relationship

The relationship between trinucleotide (CAG) repeat length and clinical features of Huntington's disease

1993 ◽  
Vol 4 (4) ◽  
pp. 398-403 ◽  
Author(s):  
Susan E. Andrew ◽  
Y. Paul Goldberg ◽  
Berry Kremer ◽  
Håkan Telenius ◽  
Jane Theilmann ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Clinical Features ◽  
Repeat Length ◽  
Cag Repeat ◽  
The Relationship

Trinucleotide repeat length instability and age of onset in Huntington's disease

1993 ◽  
Vol 4 (4) ◽  
pp. 387-392 ◽  
Author(s):  
M. Duyao ◽  
C. Ambrose ◽  
R. Myers ◽  
A. Novelletto ◽  
F. Persichetti ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Trinucleotide Repeat ◽  
Age Of Onset ◽  
Repeat Length

scholarly journals A-095 Processing Speed Indicators in Juvenile Huntington’s Disease: Assessing CAG Repeat, Age of Onset, and Mood

2020 ◽  
Vol 35 (6) ◽  
pp. 888-888
Author(s):  
Goecke N ◽  
Dawson D ◽  
Choate A ◽  
Boress K ◽  
Espe-Pfeifer P ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Symptom Onset ◽  
Processing Speed ◽  
Age Of Onset ◽  
Depressive Mood ◽  
Repeat Length ◽  
Cag Repeat ◽  
Age At Diagnosis ◽  
Juvenile Huntington’S Disease

Abstract Objective In adult onset Huntington’s Disease (HD), processing speed deficits and depression can be detected in the prodromal stages. These factors, along with CAG repeat length, may be predictive of age of symptom onset. However, less is known about the relationship between the aforementioned factors for patients diagnosed with Juvenile Huntington’s Disease (JHD). The current study aimed to investigate the relationships between age of symptom onset, CAG repeat, processing speed, and mood to improve prediction of symptom manifestation for JHD patients. Method Data was analyzed from the Kids HD study and included 30 participants (age at diagnosis M = 13.6, SD = 5.4, CAG repeat mean = 69, SD = 16). Bivariate partial correlations, independent t-tests, and regression analyses examined differences in processing speed across CAG repeat, age of onset, and depressive symptomology. Results CAG repeat length significantly predicted the natural log of age at diagnosis, β = −.59, t(25) = −3.59, p &lt; .01, and significantly explained variance in the natural log of age at diagnosis, R2 = .35, F(1, 25) = 12.86, p &lt; .01. Finally, results indicated that CAG repeat length also predicted processing speed abilities when controlling for depressed mood symptomology, R2 = .39, F(3,24) = 5.18, p &lt; .01. Conclusion CAG repeat length holds predictive power for the age of diagnosis and for processing speed, even when accounting for covariate depressive mood indicators. Overall, results indicate evidence of impacted processing speed abilities given expansive CAG repeat numbers. This is consistent with a subcortical neurodegenerative process, such as HD.

scholarly journals A Huntington’s disease (HD) phenocopy leads to the identification of the HD toxin as polyalanine. The relationship between repeat length and age of onset can be reframed as a rate equation and the toxic polyalanine length is found to be about 30.6.

2019 ◽  
Author(s):  
Eugen Tarnow
Keyword(s):  
Rate Equation ◽  
Age Of Onset ◽  
Repeat Sequence ◽  
Repeat Length ◽  
Cag Repeat ◽  
Reading Frame ◽  
The Third ◽  
Repeat Expansions ◽  
First Time ◽  
The Relationship

Huntington&rsquo;s disease (HD) is one of the most well defined &ldquo;repeat diseases&rdquo;, associated with a short repeated genetic sequence, CAG.First, taking into account that a phenocopy of HD has a different repeat that is associated with a different gene, I suggest that the gene is not important for HD, only the repeat sequence is important, in agreement with Lee et al (2019) who reached the same conclusion using a GWAS technique.Second, taking into account that a phenocopy of HD has a CTG repeat rather than a CAG repeat, and that the toxin should be the same for both disease types and that the third base in a codon is the least important, I suggest that the reading frame is shifted for the repeat expansions and that the A/T substitution takes place on the third base. The most likely sense and antisense reading frames are then (GCA)n and (GCT)n and (GCT)n and (GCA)n and the corresponding amino acid is polyalanine.Third, the more repeats, the earlier the HD onset (Brinkman et al, 1997; Wexler, 2004). I suggest that this relationship can be thought of as a rate equation. If the concentration is proportional to the probability of creating a polyalanine of length m in a repeat expansion of length n, the corresponding equation is borne out by the data on age of onset and repeat length and m is found to be about 30.6. This explains for the first time, at least approximately, why HD is not active unless there are at least 36 CAG repeats.If true, HD may be the first disease where frameshifting is the cause of the disease.

scholarly journals A Huntington’s Disease (HD) Phenocopy Leads to the Identification of the HD Toxin as Polyalanine. The Relationship Between Repeat Length and Age of Onset Can Be Reframed as a Rate Equation and the Toxic Polyalanine Length Is Found to Be about 30.6.

2019 ◽  
Author(s):  
Eugen Tarnow
Keyword(s):  
Rate Equation ◽  
Age Of Onset ◽  
Repeat Sequence ◽  
Repeat Length ◽  
Cag Repeat ◽  
Reading Frame ◽  
The Third ◽  
Repeat Expansions ◽  
First Time ◽  
The Relationship

Huntington&rsquo;s disease (HD) is one of the most well defined &ldquo;repeat diseases&rdquo;, associated with a short repeated genetic sequence, CAG.First, taking into account that a phenocopy of HD has a different repeat that is associated with a different gene, I suggest that the gene is not important for HD, only the repeat sequence is important, in agreement with Lee et al (2019) who reached the same conclusion using a GWAS technique.Second, taking into account that a phenocopy of HD has a CTG repeat rather than a CAG repeat, and that the toxin should be the same for both disease types and that the third base in a codon is the least important, I suggest that the reading frame is shifted for the repeat expansions and that the A/T substitution takes place on the third base. The most likely sense and antisense reading frames are then (GCA)n and (GCT)n and (GCT)n and (GCA)n and the corresponding amino acid is polyalanine.Third, the more repeats, the earlier the HD onset (Brinkman et al, 1997; Wexler, 2004). I suggest that this relationship can be thought of as a rate equation. If the concentration is proportional to the probability of creating a polyalanine of length m in a repeat expansion of length n, the corresponding equation is borne out by the data on age of onset and repeat length and m is found to be about 30.6. This explains for the first time, at least approximately, why HD is not active unless there are at least 36 CAG repeats.If true, HD may be the first disease where frameshifting is the cause of the disease.

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