Huntington’s Disease (HTT Gene Test) – Symptoms, CAG Ranges & Guide

Overview

The Huntington’s Disease (HTT Gene Mutation Test) is a specialized genetic test used to detect abnormal changes in the HTT gene, which is located on chromosome 4. This gene carries a sequence of DNA called CAG repeats. In healthy individuals, this sequence appears a limited number of times. But in people with Huntington’s disease, the number of CAG repeats becomes unusually high.

When these CAG repeats expand beyond the normal range, they cause damage to brain cells over time. This leads to movement problems, psychiatric symptoms, and cognitive decline. Huntington’s disease is progressive, meaning symptoms worsen with age, and it is inherited in an autosomal dominant pattern—meaning only one wrong copy of the gene is enough to cause the condition.

The HTT Gene Mutation Test helps in:

• Diagnosing Huntington’s disease in people who already show symptoms.
• Predicting whether a person may develop the disease in the future.
• Identifying carriers in families with a known history.
• Prenatal and preimplantation genetic testing to prevent transmission to the next generation.

Understanding the HTT Gene

The HTT gene gives instructions for making the huntingtin protein, a very important protein found in almost all tissues of the body. However, it plays a particularly crucial role in the brain, especially in the basal ganglia and cerebral cortex—two areas responsible for movement coordination, emotions, and decision-making.

Where huntingtin protein is produced

• Produced inside neurons (nerve cells) throughout the brain
• Also present in other organs but most important for brain development and survival
• The abnormal huntingtin protein created by expanded CAG repeats becomes toxic, damaging neurons slowly and irreversibly

As the mutated protein builds up, brain structures begin to shrink, leading to the classic symptoms of Huntington’s disease.

Main Functions and Importance of Huntingtin Protein

Although scientists continue to learn more about huntingtin protein, these functions are well established:

1. Brain development

It supports proper formation and growth of the brain before birth and during childhood.

2. Neuron survival

Huntingtin protects nerve cells from stress and helps them maintain long-term health.

3. Intracellular transport

The protein helps move nutrients, chemicals, and signals inside neurons—keeping them active and connected.

4. Gene regulation

It influences the activity of several genes needed for healthy brain function.

Why the Test is Important

The HTT gene test is crucial for:

• Confirming diagnosis when symptoms match Huntington’s disease
• Predictive testing in adults with a family history
• Carrier testing before planning a pregnancy
• Prenatal and preimplantation testing
• Providing families with accurate genetic counseling

This test gives clarity, helps in planning future medical care, and guides personal and family decisions.

Causes of Low / Negative Levels (Normal Result)

A negative or normal result means that the number of CAG repeats in the HTT gene is ≤26 repeats. This indicates:

• No abnormal CAG expansion
• No risk of developing Huntington’s disease
• No risk of passing the disease-causing mutation to children

People with normal repeat counts have a fully functioning HTT gene and will never develop symptoms of Huntington’s disease.

Symptoms or Effects of Low / Normal Levels

If the test is negative:

• No Huntington’s-related movement problems
• No cognitive decline due to this condition
• No psychiatric symptoms caused by Huntington’s
• No increased risk to family members from this individual

A negative result brings reassurance and ends uncertainty for many individuals.

Causes of High / Positive Levels (Abnormal Result)

A positive result means an expanded number of CAG repeats is present. The interpretation depends on the repeat count range:

27–35 repeats (Intermediate)

• Person will not develop Huntington’s disease
• But may pass a larger expansion to children
• Considered “unstable” repeats

36–39 repeats (Reduced Penetrance)

• Some individuals develop the disease
• Others may never develop symptoms
• Onset may be mild or late

≥40 repeats (Full Mutation)

• Person will definitely develop Huntington’s disease
• Higher number of repeats usually means earlier onset and faster progression

The test also helps determine age of onset and severity, although not with 100% accuracy.

Symptoms of High / Positive Levels

Symptoms usually begin between 30–50 years, but can appear earlier (juvenile onset) or later (senior age).

1. Movement Symptoms

• Involuntary jerking movements (chorea)
• Muscle stiffness and rigidity
• Poor balance and coordination
• Slow or abnormal walking
• Difficulty with swallowing and speech

2. Cognitive Symptoms

• Memory problems
• Slowed thinking
• Difficulty organizing tasks
• Poor judgment
• Dementia in advanced stages

3. Psychiatric / Behavioral Symptoms

• Depression
• Anxiety
• Irritability
• Mood swings
• Aggression or impulsivity
• Loss of motivation
• In rare cases, hallucinations or psychosis

These symptoms gradually worsen over years, requiring long-term care and support.

Reference Ranges

These ranges are internationally accepted standards used across genetic labs.

Sample Type and Testing Method

• The test requires a blood sample
• DNA is extracted from white blood cells
• Testing methods include:
  • PCR (Polymerase Chain Reaction)
  • Fragment Analysis

These tests accurately count the number of CAG repeats in the HTT gene.

Test Preparation

• No fasting required
• No special dietary restrictions
• Inform the doctor if you are pregnant (for prenatal testing)
• Genetic counseling is strongly recommended before and after the test
• Carry detailed family history if possible

When to Consult a Doctor

You should meet a neurologist or genetic counselor if:

• You have a family history of Huntington’s disease
• You notice early symptoms like involuntary movements or personality changes
• You are planning for pregnancy and want to know your genetic risk
• A family member recently tested positive
• You need emotional support or counseling about test results

This test has psychological impact, so professional guidance is important.

Important Word Explanations

• CAG Repeats: A DNA sequence repeated many times; higher numbers cause disease.
• Autosomal Dominant: Only one mutated gene copy is enough to cause disease.
• Chorea: Involuntary, dance-like jerking movements.
• Basal Ganglia: Brain region controlling movement.
• Penetrance: Likelihood that a gene mutation will cause symptoms.
• Prenatal Testing: Testing done during pregnancy to check genetic disorders.

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