Skip to main content
AAN.com
ARTICLES
February 1, 1996

Trinucleotide repeat length and clinical progression in Huntington's disease

February 1996 issue
46 (2) 527-531

Abstract

We examined the relationship between length of the trinucleotide (CAG) repeat at IT-15 and clinical progression of Huntington's disease in 46 mildly to moderately affected patients over a 2-year interval. Patients were divided into those with short mutations (37 to 46 repeats; n equals 25) and those with long mutations (more than equals 47 repeats, n equals 21). Patients with long repeat lengths had earlier age at onset and were younger and less functionally impaired than those with short repeats at the initial visit, but the groups did not differ in severity of neurologic or cognitive impairment. However, the long-repeat group displayed significantly greater decline in both neurologic and cognitive functioning over the 2-year follow-up period. The length of the CAG repeat correlated highly with age at onset (r equals minus 0.72, p less than 0.001) and was a strong predictor of decline in both neurologic and cognitive function. The mechanism of gene action, and the means by which longer expansions result in a more malignant disease process, remain to be elucidated.
NEUROLOGY 1996,46 527-531

Get full access to this article

View all available purchase options and get full access to this article.

REFERENCES

1.
Illarioshkin SN, Igarashi S, Onodera O, et al. Trinucleotide repeat length and rate of progression of Huntington's disease. Ann Neurol 1994;36:630-635.
2.
Huntington's Disease Collaborative Research Group. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 1993;72;971-983.
3.
And9rews SE, Goldberg YP, Kremer B, et al. Huntington's disease without CAG expansion phenocopies or errors in assignment? Am J Hum Genet 1994;54:852-863.
4.
Shoulson I, Fahn S. Huntington's disease: clinical care and evaluation Neurology 1979;29:1-3.
5.
Penney JB, Young AB, Shoulson I, et al. Huntington's disease in Venezuela: 7 years of follow-up on symptomatic and asymptomatic individuals. Mov Disord 1990;5:93-99.
6.
Myers RH, Sax DS, Koroshetz WJ, et al. Factors associated with slow progression in Huntington's disease. Arch Neurol 1991;48:800-804.
7.
Hodges JR, Salmon DP, Butters N. Differential impairment of semantic and episodic memory in Alzheimer's and Huntington's diseases: a controlled prospective study. J Neurol Neurosurg Psychiatry 1990;53:1089-1095.
8.
Folstein SE, Leigh RJ, Parhad IM, Folstein MF. The diagnosis of Huntington's disease Neurology 1986;36:1279-1283.
9.
Folstein SE Huntington's disease: a disorder of families. Baltimore Johns Hopkins University Press, 1989.
10.
Harper PS, ed Huntington's disease. London: WB Saunders, 1991.
11.
Folstein MF, Folstein SE, McHugh PR `Mini-Mental State': a practical method for grading the mental state of patients for the clinician. J Psychiatr Res 1975;12:189-198.
12.
Folstein SE, Jensen B, Leigh RJ, Folstein MF. The measurement of abnormal movement: methods developed for Huntington's disease. Neurobehav Toxicol Teratol 1983;5:605-609.
13.
Bylsma FW, Rothlind J, Hall MR, et al. Assessment of adaptive function in Huntington's disease. Mov Disord 1993;8:183-190.
14.
.Wechsler D. Wechsler Adult Intelligence Scale-Revised, manual New York: The Psychological Corporation, 1981.
15.
Schretlen DS, Bobholz JH. Standardization and initial validation of a brief test of executive attentional ability [abstract]. J Clin Exp Neuropsychol 1992;14:65.
16.
Benton AL, Hamsher K deS. Multilingual Aphasia Examination Iowa City University of Iowa, 1978.
17.
Beery KE. Revised administration, scoring, and teaching manual, the Developmental Test of Visual-Motor Integration. Cleveland: Modern Curriculum Press, 1989.
18.
Brandt J. The Hopkins Verbal Learning Test: development of a new memory test with six equivalent forms. Clin Neuropsychol 1991;5:125-142.
19.
Stroop JR. Studies of interference in serial verbal reactions. J Exper Psychol 1935;18:643-662.
20.
Reitan RM. Validity of the Trail Making Test as an indication of organic brain damage. Percept Motor Skills 1958;8:271-276.
21.
Berg EA. A simple objective test for measuring flexibility in thinking. J Gen Psychol 1948;39:15-22.
22.
Heaton RK. The Wisconsin Card Sorting Test, manual. Odessa, FL Psychology Assessment Resources, 1981.
23.
Brandt J. Cognitive investigations in Huntington's disease. In: Cermak L, ed Neuropsychological explorations of memory and cognition: essays in honor of Nelson Butters. New York: Plenum Press, 1994.
24.
Stine OC, Pleasant N, Franz ML, et al. Correlation between onset age of Huntington's disease and the length of the trinucleotide repeat in IT-15 Hum Mol Genet 1993;2:1247-1549.
25.
Sambrook J, Fritsch EF, Maniatis T. Molecular cloning a laboratory manual. 2nd ed New York: Cold Spring Harbor Laboratory Press, 1989.
26.
Andrew SE, Goldberg YP, Kremer B, et al. The relationship between trinucleotide (CAG) repeat length and clinical features of Huntington's disease. Nat Genet 1993;4:398-403.
27.
Duyao M, Ambrose C, Myers R, et al. Trinucleotide repeat length instability and age of onset in Huntington's disease. Nat Genet 1993;4:387-392.
28.
Kremer B, Squitieri F, Telenius H, et al. Molecular analysis of late-onset Huntington's disease. J Med Genet 1993;30:991-995.
29.
Snell RG, MacMillan JC, Cheadle JP, et al. Relationship between trinucleotide repeat expansion and phenotypic variation in Huntington's disease. Nat Genet 1993;4:393-397.
30.
Jodice C, Malaspina P, Persichetti F, et al. Effect of trinucleotide repeat length and parental sex on phenotypic variation in spinocerebellar ataxia 1. Am J Hum Genet 1994;54:959-965.

Information & Authors

Information

Published In

Neurology®
Volume 46Number 2February 1996
Pages: 527-531
PubMed: 8614526

Publication History

Published online: February 1, 1996
Published in print: February 1996

Permissions

Request permissions for this article.

Authors

Affiliations & Disclosures

From the Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD.
Supported in part by grant NS16735 from the National Institute of Neurological Disorders and Stroke to The Johns Hopkins University.
Received March 15, 1995. Accepted in final form May 30, 1995.
Address correspondence and reprint requests to Dr Jason Brandt, Department of Psychiatry and Behavioral Sciences, Meyer 218, The Johns Hopkins Hospital, 600 N Wolfe Street, Baltimore, MD 21287-7218.

Metrics & Citations

Metrics

Citations

Download Citations

If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Select your manager software from the list below and click Download.

Cited By
  1. Restoration of Sleep and Circadian Behavior by Autophagy Modulation in Huntington's Disease, The Journal of Neuroscience, 43, 26, (4907-4925), (2023).https://doi.org/10.1523/JNEUROSCI.1894-22.2023
    Crossref
  2. Behavioral Abnormalities and Cognitive Impairment in Rare Dementia Syndromes, Progressive Supranuclear Palsy, Huntington Disease and Sporadic Creutzfeldt-Jakob Disease, Encyclopedia of Behavioral Neuroscience, 2nd edition, (115-130), (2022).https://doi.org/10.1016/B978-0-12-819641-0.00011-6
    Crossref
  3. Gender Differences in Non-sex Linked Disorders: Insights From Huntington's Disease, Frontiers in Neurology, 11, (2020).https://doi.org/10.3389/fneur.2020.00571
    Crossref
  4. Baseline Variables Associated with Functional Decline in 2CARE, A Randomized Clinical Trial in Huntington’s Disease, Journal of Huntington's Disease, 9, 1, (47-58), (2020).https://doi.org/10.3233/JHD-190391
    Crossref
  5. CAG Repeat Size Influences the Progression Rate of Spinocerebellar Ataxia Type 3 , Annals of Neurology, 89, 1, (66-73), (2020).https://doi.org/10.1002/ana.25919
    Crossref
  6. Does Late-Onset Huntington Disease Represent a Distinct Symptomatic Picture? Evidence for a Selective Deficit in Executive Function and Emotion Recognition, in the Absence of Behavioral and Psychiatric Disorders, Journal of Intellectual Disability - Diagnosis and Treatment, 7, 4, (243-250), (2019).https://doi.org/10.6000/2292-2598.2019.07.04.7
    Crossref
  7. Impaired Redox Signaling in Huntington’s Disease: Therapeutic Implications, Frontiers in Molecular Neuroscience, 12, (2019).https://doi.org/10.3389/fnmol.2019.00068
    Crossref
  8. Association Between Toll‐Like Receptor 4 ( TLR4 ) and Triggering Receptor Expressed on Myeloid Cells 2 ( TREM2 ) Genetic Variants and Clinical Progression of Huntington's Disease , Movement Disorders, 35, 3, (401-408), (2019).https://doi.org/10.1002/mds.27911
    Crossref
  9. Molecular Pathogenesis in Huntington’s Disease, Biochemistry (Moscow), 83, 9, (1030-1039), (2018).https://doi.org/10.1134/S0006297918090043
    Crossref
  10. Neuroprotective effect of naringin, a flavone glycoside in quinolinic acid-induced neurotoxicity: Possible role of PPAR-γ, Bax/Bcl-2, and caspase-3, Food and Chemical Toxicology, 121, (95-108), (2018).https://doi.org/10.1016/j.fct.2018.08.028
    Crossref
  11. See more
Loading...

View Options

Get Access

Login options

Check if you have access through your login credentials or your institution to get full access on this article.

Personal login Institutional Login
Purchase Options

Purchase this article to access the full text.

Purchase Access, $39 for 24hr of access

View options

Full Text

View Full Text

Full Text HTML

View Full Text HTML

Media

Figures

Other

Tables

Share

Share

Share article link

Share