The Genetics of HD

How is Huntington disease inherited?
Huntington disease (HD) is caused by an abnormality in the hungintin gene, which is located on chromosome 4. Each of us has two copies of this gene. One copy is inherited from our mother and the other copy is inherited from our father. HD is caused by a change in one of these two copies. A disease that is caused when only one of the two copies of the gene is abnormal is called "autosomal dominant."

As a result, most individuals with HD also have a parent who had the abnormal gene and was diagnosed with the disease. The children of an individual with HD are at 50% risk of inheriting the abnormal huntingtin gene from their parent with the disease.

Most families with HD report a long history with this disease, with each generation having some individuals diagnosed with the disease.

What is the change in the huntingtin gene that causes HD?
Within the huntingtin gene, there is a sequence of DNA that has a variable number of CAG repeats. This sequence of 3 nucleotides codes for an amino acid called glutamine. In a person with Huntington disease, the change in the huntingtin gene that causes the clinical symptoms of the disease is an increased number of CAG nucleotides. The chart below explains the interpretation of various numbers of CAG repeats in the huntingtin gene.

Number of CAG Repeats Result

26 or below   Normal
27-35   Person normal but child may develop Huntington disease
36-39   Person more likely to develop Huntington disease
40 and above   Person will develop Huntington disease – 100% diagnosis

In general, persons who have 40 or more CAG repeats in their gene will develop Huntington disease unless they die of other causes before disease signs and symptoms appear. Persons having 36-39 CAG repeats may or may not develop HD during their lifetime, but their children are at greater risk for having the disease. Individuals with 27-35 CAG repeats are not at risk for Huntington disease, but their children might be at risk for developing symptoms.

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