Huntington's disease (HD) is a hereditary neurodegenerative disorder characterized by the progressive loss of motor control, cognitive decline, and psychiatric symptoms. This article aims to provide an informative guide to the genetics of Huntington's disease, including an overview of the causative genetic mutation, inheritance patterns, genetic testing, and potential therapeutic approaches.
HD is caused by a mutation in the huntingtin (HTT) gene located on chromosome 4. This mutation involves an abnormal expansion of a trinucleotide repeat sequence, specifically CAG (cytosine-adenine-guanine). Normal individuals have 10-35 CAG repeats, while individuals with HD have more than 40 CAG repeats. The expanded CAG repeats result in the production of an abnormal protein called mutant huntingtin (mHTT), which leads to the characteristic neurodegeneration observed in HD.
HD follows an autosomal dominant pattern of inheritance. This means that individuals who inherit a single mutant HTT gene from either parent will develop the disease. Every child of an affected individual has a 50% chance of inheriting the disease-causing mutation.
Genetic testing for HD involves analyzing the number of CAG repeats in the HTT gene. This test can be performed prenatally, in individuals at risk, or after the onset of symptoms. It is crucial to obtain genetic counseling before and after testing to understand the implications of the results and make informed decisions.
Predictive testing is offered to asymptomatic individuals who are at risk of inheriting the HD mutation. This type of testing helps identify whether they carry the expanded CAG repeats and may develop HD in the future. It is a personal decision that should be made after careful consideration of the potential psychological and social implications.
PGD is a reproductive option for couples at risk of transmitting the HD mutation to their offspring. It involves in vitro fertilization (IVF), where embryos created outside the body undergo genetic testing before being implanted in the uterus. This technique allows the selection of embryos without the HD mutation, reducing the risk of passing on the disease.
While there is currently no cure for HD, several therapeutic approaches are being explored:
Understanding the genetics of Huntington's disease is crucial for accurate diagnosis, genetic counseling, and the development of potential therapies. The causative mutation in the HTT gene, inheritance patterns, genetic testing options, and emerging therapeutic approaches provide hope for future advancements in managing and treating this devastating neurodegenerative disorder.