Related Experiment Video
Updated: Jan 24, 2026
An Allele-specific Gene Expression Assay to Test the Functional Basis of Genetic Associations
Published on: November 3, 2010
Clinical phenotype in carriers of intermediate alleles in the huntingtin gene
Daniel Savitt1, Joseph Jankovic1
1Parkinson's Disease and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX, United States.
Insights
Individuals with intermediate allele (IA) CAG repeat lengths in the huntingtin gene may show symptoms similar to Huntington disease (HD). These findings highlight the need for careful genetic counseling and monitoring for potential HD development.
Area of Science:
- Genetics
- Neurology
- Molecular Biology
Background:
- Huntington disease (HD) is a genetic disorder caused by CAG repeat expansions in the huntingtin (HTT) gene.
- Individuals with intermediate allele (IA) CAG repeat lengths (27-35 repeats) may exhibit clinical, imaging, and pathological signs overlapping with HD.
- Approximately 6% of the general population carries IA CAG repeats in at least one HTT gene allele, posing challenges for genetic counseling.
Purpose of the Study:
- To characterize the clinical phenotype of individuals with intermediate allele (IA) CAG repeat lengths in the huntingtin (HTT) gene.
- To evaluate the range of symptoms, including motor, psychiatric, and cognitive, in individuals with IA CAG repeats.
Main Methods:
- Retrospective review of medical records for patients with IA CAG repeats at the Parkinson's Disease Center and Movement Disorders Clinic (PDCMDC).
- Assessment of age at symptom onset, dominant clinical features, and presence of psychiatric and cognitive symptoms.
- Analysis of HTT gene CAG repeat lengths ranging from 27 to 35.
Main Results:
- Nine individuals (4 males, 5 females) with IA CAG repeats (27-35) were identified.
- Symptom onset ranged from 27 to 78 years.
- Motor symptoms included chorea (6), gait disturbance (3), stereotypies (2), and motor tics (1).
- All nine patients exhibited psychiatric symptoms, with depression being most prevalent.
Conclusions:
- Individuals with IA CAG repeats in the HTT gene present with diverse motor and non-motor symptoms that overlap with the HD phenotype.
- These individuals and their offspring should be considered at risk for developing progressive HD.
- The study underscores the importance of recognizing IA CAG repeats as a potential risk factor for HD.
Objective:
To describe the phenotype of individuals with intermediate allele (IA) CAG repeat length in the huntingtin (HTT) gene evaluated at the Parkinson's Disease Center and Movement Disorders Clinic (PDCMDC) at Baylor College of Medicine (BCM).
Background:
Huntington disease (HD) is caused by a mutation in the HTT gene of 36 or more CAG trinucleotide repeats. Since our original case report of pathologically proven HD with 29 CAG repeats, a growing body of evidence has accumulated supporting the observation that individuals with IA (27 to 35 CAG repeats) may exhibit clinical, imaging, and pathologic manifestations of HD. About 6% of the general population has CAG repeats in the IA range in at least one allele of the HTT gene. The presence of IA is a challenge for genetic counseling.
Methods:
Medical records of patients with IAs seen at the PDCMDC at BCM from January 2008 to the present were reviewed to assess age at symptom onset, dominant clinical features and presence of psychiatric and cognitive symptoms.
Results:
Four men and five women were found to have IAs (range: 27-35) in the course of their evaluation at the PDCMDC. The age at onset of clinically evident symptoms ranged from 27 to 78 years. Six individuals had chorea, three had gait disturbance, two had stereotypies, and one patient had multiple motor tics. All nine had psychiatric symptoms, with depression being the most common.
Conclusion:
Our series of 9 individuals with IA in the HTT gene exhibit a variety of motor and non-motor features that overlap with the HD phenotype. These individuals and their offspring should be considered at risk for development of progressive HD.
Related Concept Videos
01:49Multiple Allele Traits
01:24Electron Carriers
Over the many stages of cellular respiration, glucose breaks down into carbon dioxide and water. Electron carriers pick up electrons lost by glucose in these reactions, temporarily storing and releasing them into the electron...
02:41Lethal Alleles
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
01:35Disassembly of Intermediate Filaments
Keratin proteins, found at the cell periphery near cell junctions, undergo a cycle of assembly and disassembly. In Type...
01:31Types of Intermediate Filaments
00:57Formation of Intermediate Filaments