Huntington's disease (HD) is a neurological condition caused by the inheritance of a faulty gene that interferes with the functioning of the protein huntingtin inside brain cells. Children with a parent who has the HD gene have a 50 per cent risk of developing the disease. HD isn't apparent at birth and symptoms first tend to appear somewhere around middle age. There is no cure.
Huntington’s disease (HD) is a neurological condition caused by the inheritance of a defective gene. The faulty gene interferes with the functioning of a particular protein, called ‘huntingtin’, inside brain cells, leading to progressive loss of cognitive, physical and emotional function.
Physical symptoms include twitching, lack of coordination and difficulties with speech and swallowing. Cognitive (thought-related) symptoms include short-term memory loss and concentration problems. Emotional symptoms include mood swings, apathy and aggression.
Children with a parent who has the HD gene have a 50 per cent risk of developing the disease. HD isn’t apparent at birth and symptoms first tend to appear somewhere around middle age. There is no cure.
Genes and chromosomes
Genes are the blueprint for our bodies. Almost every cell in the human body contains a copy of the blueprint, which is stored on chromosomes inside a special sac called the nucleus. The chromosomes are long strands of a chemical substance called deoxyribonucleic acid (DNA). Humans have 46 paired chromosomes, with two sex chromosomes that decide gender and 44 chromosomes that dictate other factors. Genes are beaded along these chromosome strands.
HD is an autosomal dominant condition. This means that the HD gene isn’t located on the sex chromosomes (so both males and females can be affected). Also, the child needs to inherit only one HD gene from either parent to develop the disease. (In contrast, ‘recessive’ conditions – unlike HD – require the child to inherit the faulty gene from both parents.)
Triplet repeat mutation
The HD gene (or IT15 gene), located on chromosome number four, interferes with the manufacture of a particular protein known as huntingtin.
Genes are made up of chemical bases known as nucleotides. The different types of nucleotides include adenine (A), cytosine (C), guanine (G) and thymine (T). Each gene consists of three nucleotides in series (‘triplets’). Different triplets prompt the production of different amino acids, which are the building blocks of proteins. Proteins are crucial to biological activities inside the body.
The DNA sequence cytosine–adenine–guanine (CAG) is the genetic ‘code’ for the production of the protein huntingtin. A person with 28 or fewer repeats of the CAG sequence will not develop HD, nor will their children. Everyone with 40 or more CAG repeat sequences will develop HD and their children will have a 50 per cent risk of developing HD. This excessive repetition of DNA is known as a triplet repeat mutation.
It appears that people who have 29–35 repeats will not develop HD themselves, but a small percentage of their children may. Whereas people with repeats in the range of 36–39 are considered to be in the ‘grey zone’; they may or may not develop HD and, likewise, their children may or may not be affected by the mutant gene. (It is important to note that different laboratories may slightly vary these interpretations.)
The protein huntingtin
The protein huntingtin is comprised of amino acids strung together. One part of the chain consists of the amino acid glutamine. In people without HD, this section ranges between 12 and 34 glutamines in length, while a person with HD has a section of more than 35 glutamines. (Abnormally long chains of glutamine are also associated with a number of other neurological conditions.)
The protein huntingtin appears to be crucial for proper brain functioning, although researchers are still trying to uncover its exact roles. Evidence suggests that the huntingtin protein in people with HD tends to break into pieces, which then clump together. These protein clumps build up inside the nuclei of brain cells, which either impairs their functioning or kills them. The cause of the clumping remains a mystery, but it is thought that the excessive chain of glutamine alters the way huntingtin interacts with other proteins inside the brain cell.
Risks of inheritance
Each child of a person with HD has a 50 per cent chance of inheriting the condition themselves. Since the HD gene isn’t located on a sex chromosome, males and females are equally at risk. If a person has inherited the HD gene from one of their parents, they will develop the disease if they live long enough.
Genetic tests and counselling are available. A small percentage of HD cases occur with no family history of the disease. One theory suggests that the CAG sequence that governs the production of the huntingtin protein may lengthen (or ‘repeat’) by accident during subdivision of DNA in newly formed sperm or egg cells.
Where to get help
- Your doctor
- Genetic counsellor
- Huntington’s Victoria Tel. (03) 9818 6333
Things to remember
- Huntington’s disease (HD) is a neurological condition caused by the inheritance of a defective gene.
- HD is an autosomal dominant condition, which means both males and females can be affected and the child needs to inherit only one HD gene to develop the disease.
- The HD gene interferes with the manufacture of a particular protein known as huntingtin, which appears to be crucial for proper brain functioning.
- There is no cure.
You might also be interested in:
- Genetic services in Victoria.
- Huntington's disease.
- Huntington's disease - behavioural problems.
- Huntington's disease - diet issues.
- Huntington's disease - genetics.
- Nervous system.
- Neuromuscular system.
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Last reviewed: June 2011
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