Angelman syndrome is a complex genetic disorder affecting approximately 1 in 15,000 children worldwide. It can result in serious physical and mental disabilities, most of which will not improve as the patient ages. There is currently no cure for Angelman syndrome.
The condition is caused by a genetic mutation that occurs soon after the affected child is conceived, but the disorder generally is not diagnosed until the child is between the ages of 18 months and 6 years old. Angelman syndrome is generally believed to be random and not hereditary, but researchers have seen a small rate of recurrence (approximately 1 percent greater risk than the general population) within families.
All babies receive their genes in pairs, one copy coming from each parent. Most cells in the body use both the genes from the mother, known as the maternal copy, and from the father, known as the paternal copy, to complete regular cellular functions. However, in specific regions of the brain, only the maternal UBE3A gene is active, and the paternal gene is turned off and cannot be used.
When the maternal UBE3A gene is dysfunctional, the brain cells do not have the instructions typically provided by the gene, so the patient experiences a number of serious neurological symptoms and associated illnesses. There are several known reasons for the maternal UBE3A gene to be dysfunctional, including chromosome deletions, imprinting errors, paternal uniparental disomy, and mutations in the UBE3A gene. In roughly 10 percent of cases, no specific cause for Angelman syndrome can be identified.
About 70 percent of Angelman syndrome cases can be attributed to the microdeletion of a region of the maternal chromosome 15, where the UBE3A gene resides. Genetic microdeletions are typically irregular processes that are not hereditary.
In around 1 percent of microdeletion incidences, the deleted chromosome segment may be rearranged. In the case of Angelman syndrome, a segment of the maternal chromosome 15 containing the UBE3A gene breaks off and reattaches to a different chromosome location, disrupting the function of other genes and potentially causing other diseases.
Genomic imprinting is the process by which one copy the same gene is preferentially silenced. This could either be the maternal or the paternal copy of the gene. Genomic imprinting is essential for healthy development in many areas of the body. Erroneous imprinting can cause Angelman syndrome by inactivating part of the maternal chromosome 15 where the UBE3A gene resides. Researchers have found that imprinting errors cause from 3 to 5 percent of Angelman syndrome cases. The causes of imprinting defects are not well understood.
Paternal uniparental disomy
About 2 to 5 percent of Angelman syndrome cases happen when a child inherits both copies of chromosome 15 from the father, meaning there is no maternal copy of chromosome 15. This phenomenon, called uniparental disomy, can occur with any chromosome, but only paternal uniparental disomy of chromosome 15 causes Angelman syndrome.
UBE3A gene mutations
Mutations in the maternal UBE3A gene are the cause of about 10 to 20 percent of Angelman syndrome cases. In such cases, the UBE3A gene has abnormal changes that cause the gene to malfunction, preventing it from working effectively.
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