Multiple clinical features of Huntington’s disease correlate with mutant HTT gene CAG repeat lengths and neurodegeneration

@article{Podvin2018MultipleCF,
  title={Multiple clinical features of Huntington’s disease correlate with mutant HTT gene CAG repeat lengths and neurodegeneration},
  author={Sonia Podvin and Holly T. Reardon and Katrina Yin and Charles Mosier and Vivian V. H. Hook},
  journal={Journal of Neurology},
  year={2018},
  volume={266},
  pages={551-564}
}
Huntington’s disease (HD) is a fatal neurodegenerative disease caused by mutant HTT gene expansions of CAG triplet repeat numbers that are inherited in an autosomal dominant manner. [] Key Result Quantitative HTT gene expression patterns analyzed in normal adult human brain regions demonstrated its distribution in areas known to undergo neurodegeneration in HD, as well as in other brain regions. Future investigation of the relationships of the spectrum of clinical HD features with mutant HTT molecular…

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References

SHOWING 1-10 OF 84 REFERENCES

Huntington disease

TLDR
The genetic and clinical diagnosis of the condition, its clinical assessment and the multidisciplinary management of symptoms, given the absence of effective disease-modifying therapies are described, as well as the concept of genetic modifiers of the disease.

Weight loss in Huntington disease increases with higher CAG repeat number

TLDR
Weight loss in Huntington disease (HD) is directly linked to CAG repeat length and is likely to result from a hypermetabolic state and could lead to effective energy-based therapeutics.

WEIGHT LOSS IN HUNTINGTON DISEASE INCREASES WITH HIGHER CAG REPEAT NUMBER

TLDR
Weight loss in Huntington disease (HD) is directly linked to CAG repeat length and is likely to result from a hypermetabolic state and could lead to effective energy-based therapeutics.

Homozygosity in Huntington’s disease

TLDR
The clinical, neuropsychological, and molecular characterisation of such a patient in comparison to his heterozygous brother is reported, since homozygous carriers of the disease are no more severely affected than heterozygouse carriers.

Trinucleotide repeat length and progression of illness in Huntington's disease.

TLDR
It is suggested that the CAG repeat length may influence or trigger the onset of HD, but other genetic, neurobiological, or environmental factors contribute to the progression of illness and the underlying pace of neuronal degeneration.

Pathogenic mechanisms in Huntington's disease.

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

TLDR
An analysis of data from the Coenzyme Q10 and Remacemide Evaluation in Huntington's Disease (CARE‐HD) clinical trial shows that longer CAGn is associated with greater clinical progression of HD, and adjusting for age shows this finding may account for the variable results from previous studies examining CAGm.

Age, CAG repeat length, and clinical progression in Huntington's disease

TLDR
Controlling for age of onset increased the correlation between CAG repeat length and progression of all variables by 69% to 159%.
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