Understanding Genetic Classes of Angelman Syndrome Dr . Charles Williams
Understanding Genetic Classes of Angelman Syndrome Dr . Charles Williams
Conducting blood testing to diagnose Angelman syndrome ( AS ) can be a complicated matter . Here I summarize the different genetic causes of AS and provide general guidelines about how to use genetic tests to confirm the diagnosis of AS . First , let us look at the genetic mechanisms that cause AS :
A chromosome 15 pair is illustrated for each class depicted but the other chromosomes are not shown . The P indicates the maternally-derived chromosome and the M indicates the maternally-derived one . The shaded chromosomes have a paternal pattern of gene functioning while the unshaded chromosomes have a maternal pattern . AS can be caused by either a large chromosome deletion ( 70 % of the time ); a disruptive mutations in the UBE3A gene inherited from the mother ( indicated by the X ); inheritance from the father of 2 normal number 15 chromosomes ( e . g ., paternal uniparental disomy [ UPD ]); or an imprinting defect ( ID ), occurring when the chromosome 15 inherited from the mother has the paternal pattern of gene functioning because of a problem in the imprinting center ( denoted by the small open circle ).
In addition to these mechanisms , a clinical diagnosis of AS may be given even though the genetic testing is normal . The percentages indicate how common each mechanism occurs .
How do we use genetic testing and what is the sequence of testing ? There are many pathways to diagnosis for families undergoing testing for AS but the most common testing pathway is summarized here :
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