Autism-World

Angelman syndrome was known as a distinct clinical entity before the genetics were fully understood. It has taken years of research to elucidate the different genetic mechanisms that can lead to AS. There are 4 major genetic mechanisms that cause Angelman syndrome:

1.Chromosome 15q11 -q13 deletion (a very small piece missing) accounts for 65-75% of AS casesand has a less than 1% recurrence risk. It was first observed on high resolution chromosome analysis that some patients with AS had a very small piece missing from the long (q) arm of chromo some 15 between bands q 11-13. This led to the development of the FISH (fluorescence in-situ hybridization) test to readily diagnose this common deletion from the maternally derived chromosome 15.

2.Paternal uniparental disomy (UPD) accounts for 3-5% of AS cases and has less than I% recurrence. Patients with UPD have two paternal copies of chromosome 15 and no maternal copy of chromosome 15. These observations suggest that each copy of chromosome 15 is marked with “alabel” (an imprint) for its parental origin. This is thought to regulate expression of genes on eachchromosome 15. Thus AS represents a loss of functionally important imprinted genes on chromosome 15 that are only expressed from the maternal chromosome 15.

3.Imprinting center (IC) mutations account for 7-9% of AS cases, and can have significant recurrence. The imprinting center acts as the ’switch’ that turns on the maternal copy of the UBE3Agene and turns off the paternal copy in certain tissues of the central nervous system. If there is a mutation in the IC, it cannot perform its ’switch’ function. If the IC mutation occurs sporadically in the affected individual, the recurrence risk is less than 1%. However, if the patient’s mother carries the IC mutation on her own paternally inherited chromosome 15, there is a 50% risk of recurrence.

4.UBE3A mutations account for 6-20% of AS cases. If it happens sporadically in the affected individual, the recurrence risk is less than 1%. However, if the patient’s mother carries the UBE3A mutation on her own paternally inherited chromosome 15, there is a 50% recurrence risk. Let’s talk more about the UBE3A gene.


Technorati : Angelman Syndrome




This entry was posted on Monday, September 10th, 2007 at 4:47 pm and is filed under Angelman Syndrome.