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

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 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

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 Linking SNPs to CAG repeat length in Huntington's disease patients

2008 ◽  
Vol 5 (11) ◽  
pp. 951-953 ◽  
Author(s):  
Wanzhao Liu ◽  
Lori A Kennington ◽  
H Diana Rosas ◽  
Steven Hersch ◽  
Jang-Ho Cha ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Repeat Length ◽  
Cag Repeat

scholarly journals Conformational studies of pathogenic expanded polyglutamine protein deposits from Huntington’s disease

2019 ◽  
Vol 244 (17) ◽  
pp. 1584-1595 ◽  
Author(s):  
Irina Matlahov ◽  
Patrick CA van der Wel
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Structural Biology ◽  
Age Of Onset ◽  
Repeat Expansion ◽  
Cag Repeat ◽  
Mutant Huntingtin ◽  
Cag Repeat Expansion ◽  
Recent Developments ◽  
Mutant Huntingtin Protein

Huntington’s disease, like other neurodegenerative diseases, continues to lack an effective cure. Current treatments that address early symptoms ultimately fail Huntington’s disease patients and their families, with the disease typically being fatal within 10–15 years from onset. Huntington’s disease is an inherited disorder with motor and mental impairment, and is associated with the genetic expansion of a CAG codon repeat encoding a polyglutamine-segment-containing protein called huntingtin. These Huntington’s disease mutations cause misfolding and aggregation of fragments of the mutant huntingtin protein, thereby likely contributing to disease toxicity through a combination of gain-of-toxic-function for the misfolded aggregates and a loss of function from sequestration of huntingtin and other proteins. As with other amyloid diseases, the mutant protein forms non-native fibrillar structures, which in Huntington’s disease are found within patients’ neurons. The intracellular deposits are associated with dysregulation of vital processes, and inter-neuronal transport of aggregates may contribute to disease progression. However, a molecular understanding of these aggregates and their detrimental effects has been frustrated by insufficient structural data on the misfolded protein state. In this review, we examine recent developments in the structural biology of polyglutamine-expanded huntingtin fragments, and especially the contributions enabled by advances in solid-state nuclear magnetic resonance spectroscopy. We summarize and discuss our current structural understanding of the huntingtin deposits and how this information furthers our understanding of the misfolding mechanism and disease toxicity mechanisms. Impact statement Many incurable neurodegenerative disorders are associated with, and potentially caused by, the amyloidogenic misfolding and aggregation of proteins. Usually, complex genetic and behavioral factors dictate disease risk and age of onset. Due to its principally mono-genic origin, which strongly predicts the age-of-onset by the extent of CAG repeat expansion, Huntington’s disease (HD) presents a unique opportunity to dissect the underlying disease-causing processes in molecular detail. Yet, until recently, the mutant huntingtin protein with its expanded polyglutamine domain has resisted structural study at the atomic level. We present here a review of recent developments in HD structural biology, facilitated by breakthrough data from solid-state NMR spectroscopy, electron microscopy, and complementary methods. The misfolded structures of the fibrillar proteins inform our mechanistic understanding of the disease-causing molecular processes in HD, other CAG repeat expansion disorders, and, more generally, protein deposition disease.

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