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

@article{Duyao1993TrinucleotideRL,
  title={Trinucleotide repeat length instability and age of onset in Huntington's disease},
  author={Mabel P. Duyao and Christine M. Ambrose and Richard H. Myers and Andrea Novelletto and Francesca Persichetti and Marina Frontali and Susan E B Folstein and Christopher A. Ross and Mary L. Franz and Margaret H. Abbott and Jacqueline Gray and P. Michael Conneally and Angela Young and John B. Penney and Zane R. Hollingsworth and Ira Shoulson and Alice M. Lazzarini and Arthur Falek and Walter J. Koroshetz and DanielS. Sax and Edward Dennis Bird and Jean Paul G. Vonsattel and Ernesto Bonilla and Jose Ma. J. Alvir and J. Bickham Conde and Jang-Ho Cha and Leon Dure and Fidela Gomez and Maria Ramos and Juan R. Sanchez-Ramos and S. Robert Snodgrass and Mary de Young and N. Wexler and C. M. Moscowitz and Graciela K. Penchaszadeh and H. Macfarlane and M. A. Anderson and Barbara Jenkins and Jayalakshmi Srinidhi and Glenn T. Barnes and James F. Gusella and Marcy E. MacDonald},
  journal={Nature Genetics},
  year={1993},
  volume={4},
  pages={387-392}
}
The initial observation of an expanded and unstable trinucleotide repeat in the Huntington's disease gene has now been confirmed and extended in 150 independent Huntington's disease families. HD chromosomes contained 37–86 repeat units, whereas normal chromosomes displayed 11–34 repeats. The HD repeat length was inversely correlated with the age of onset of the disorder. The HD repeat was unstable in more than 80% of meiotic transmissions showing both increases and decreases in size with the… 

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.

Analysis of triplet repeats in the huntingtin gene in Japanese families affected with Huntington's disease.

TLDR
Strong linkage disequilibrium was found between the CAG repeat expansion and an allele of (CCG)10 in JapaneseHD chromosomes in Japanese HD chromosomes, distinct from that described previously in western populations.

Instability of CAG repeats in Huntington's disease: relation to parental transmission and age of onset.

TLDR
Several features of the expansion mutation in HD are similar to those previously observed for mutations of similar size in spinobulbar muscular atrophy and in myotonic dystrophy, and to those observed more recently in spinocerebellar ataxia type 1 and in dentatorubropallidoluysian atrophy, four diseases also caused by expansion of CAG repeats.

Trinucleotide repeat length and rate of progression of Huntington's disease

TLDR
Significant positive correlation between the rate of progression of clinical symptoms and CAG repeat length is found and suggests an important role of expanded trinucleotide repeat length in affecting the pathological process during the enitre course of Huntington's disease.

Gametic but not somatic instability of CAG repeat length in Huntington's disease.

TLDR
The data indicate that the developmental timing of repeat instability appears to differ between HD and fragile X syndrome, and that the fundamental mechanisms leading to repeat expansion may therefore be distinct.

De novo expansion of a (CAG)n repeat in sporadic Huntington's disease

TLDR
Nine families with potential de novo expression of Huntington's disease are examined, finding elderly unaffected relatives inherited the same chromosome as that containing the expanded repeat in the proband, but had repeat lengths of 34–38 units, spanning the gap between the normal and HD distributions.

Huntington ' s disease . gene in Japanese families affected with Analysis of triplet repeats in the huntingtin

TLDR
Strong linkage disequilibrium was found between the CAG repeat expansion and an allele of (CCG)1o in Japanese HD chromosomes and it has been proposed that the allele of seven repeats could be critical in Huntington's disease.

Limited Expansion of the (CAG)n Repeat of the Huntington Gene: A Premutation (?)

TLDR
The IT15 gene on chromosome 4p has been identified containing an unstable and expanded trinucleotide repeat in patients with HD and the characteristics of this repeat in 248 individuals from 41 Belgian HD families are reported on.

age of onset . disease : relation to parental transmission and Instability of CAG repeats in Huntington ' s

TLDR
An analysis of Huntington's disease mutation and the characteristics of its transmission in 36 HD families suggests several features of the expansion mutation in HD are similar to those previously observed for mutations ofsimilar size in spinobulbar muscular atrophy and in myotonic dystrophy, and to those observed more recently in spinocerebellar ataxia type 1 and in dentatorubropallidoluysian atrophy.

CAG repeat size and clinical presentation in Huntington's disease

TLDR
It is concluded that patients lacking the family history of HD frequently show no expansion of the C AG repeats, and the sex of the affected parent influences both the CAG repeat size and the phenotypic expression of the HD gene in the offspring.
...

References

SHOWING 1-10 OF 32 REFERENCES

Moderate instability of the trinucleotide repeat in spino bulbar muscular atrophy.

TLDR
Increased length of a protein-coding CAG repeat within the androgen receptor gene appears to be the only type of mutation responsible for spino-bulbal muscular atrophy (SBMA or Kennedy disease), and the mutant allele was unstable upon transmission from parent to child.

Meiotic stability and genotype – phenotype correlation of the trinucleotide repeat in X–linked spinal and bulbar muscular atrophy

TLDR
It is found that expanded (CAG)n alleles undergo alteration in length when transmitted from parent to offspring, and there was a greater rate of instability in male meiosis than in female meiosis.

Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1

TLDR
There is a direct correlation between the size of the (CAG)n repeat expansion and the age–of–onset of SCA1, with larger alleles occurring in juvenile cases.

Myotonic dystrophy mutation: an unstable CTG repeat in the 3' untranslated region of the gene.

TLDR
Increases in the size of the allele in patients with DM are now shown to be due to an increased number of trinucleotide CTG repeats in the 3' untranslated region of a DM candidate gene.

Huntington's disease: two families with differing clinical features show linkage to the G8 probe.

TLDR
Although the data support the existence of a singleHD locus, use of the G8 probe for presymptomatic testing in these kindreds would have resulted in a 12 percent error rate in genotype assignment at the HD locus.

An unstable triplet repeat in a gene related to myotonic muscular dystrophy.

TLDR
These studies suggest that the mutational mechanism leading to DM is triplet amplification, similar to that occurring in the fragile X syndrome.