Promoting Excellence : Huntington's Disease Recommendations to the Field : The Genetic Basis

Eyes with veil illustrationThe genetic mutation that causes HD is an unstable expanded trinucleotide repeat on the short arm of the 4th chromosome. In this area of the genome, the gene normally has fewer than 30 CAG repeats. When there are 40 or more CAG repeats, HD is fully penetrant. A gene is fully penetrant when all gene carriers manifest the illness. When there is reduced penetrance, some carriers may not develop signs of the illness. When there are 36 to 40 CAG repeats in the huntingtin gene, the disease is less than fully penetrant, but due to the instability in the mutation, a full-length mutation may be passed to the next generation where HD will appear. When there are 30 to 35 repeats, the carrier will not develop the disease, although a longer CAG repeat length may be transmitted to the next generation. The trinucleotide repeat instability is more pronounced in male gene carriers, which leads to the rare appearance of juvenile onset in some children of affected men (and occasionally women). Because of this inherent instability, the mutation may arise de novo in a family.

"Illness and disability are a family affair. The diagnosis that made our family member need care happened to us as well. It is our diagnosis just as much as it's theirs. I have a psychosocial form of the disease, just as my husband has a clinical one."
-A Family Member

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Promoting Excellence in End-of-Life Care was a national program of the Robert Wood Johnson Foundation dedicated to long-term changes in health care institutions to substantially improve care for dying people and their families. Visit PromotingExcellence.org for more resources.

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