Angelman syndrome is a genetic disorder that causes severe developmental delay seizures frequent laughter and Ataxia or poor control of voluntary muscle movements now it happens when a gene on chromosome 15 called Ube 3A is not expressed or transcribed in a messenger RNA Ube 3A stands for ubiquitin protein ligase e3a and the protein it codes 4 is called e6ap or E6 Associated protein the job of E6 Associated protein is to go around tagging or attaching a tiny peptide called ubiquitin to other proteins a process called ubiquitination once that happens the ubiquininated protein is degraded by the proteosome a part of the cell's recycling machinery it's kind of like painting an orange U on a tree so that a lumberjack knows which trees need to be chopped down so E6 Associated protein has an important job and it turns out that the region of chromosome 15 around ube3a is imprinted imprinting refers to gene expression that's dependent on the parent of origin of a gene this means that either the maternally derived or paternally derived copy of the gene is silenced this differs from most genes in the genome where both the maternal and paternal copies are expressed normally in the brain only the maternally derived copy of ube3a is expressed while the paternal copy is silenced unfortunately this process of imprinting leaves the maternal copy of Ube 3A vulnerable so with the paternal copy of the gene imprinted and epigenetically silenced you've only got the maternal copy left so this means that if anything happens to the maternal copy the result is Angelman syndrome there are a few different ways that Angelman syndrome can develop the most common one is a deletion of a couple million base pairs of DNA on the maternal copy of chromosome 15 which includes ube3a sometimes the deletion overlaps a nearby Gene called oca2 which codes for a pigment that gives color to the eye hair and skin as a result of this these Angelman syndrome patients can have a light complexion a second way is a mutation within the maternal copy of ube3a which makes the protein ineffective a third way to get Angelman syndrome is when the entire maternal chromosome 15 is absent and instead there's an extra copy of the paternal chromosome 15. this scenario is called paternal uniparental dysomy which means that one parent the father contributed two of the same chromosome while the mother contributed none because of this one for one exchange there isn't any aneuploidy or abnormal chromosome number but this does mean that both chromosomes are epigenetically marked as being from Dad so Ube 3A is turned off in both a final type of mutation causing Angelman syndrome is called an imprinting defect in this case the maternal chromosome 15 gets mistakenly methylated which ultimately causes the Ube 3A Gene to be silenced this might be caused as part of an error in oogenesis or egg development or because of a mutation in the imprinting Center which is an epigenetic control sequence now most cases of Angelman syndrome are sporadic meaning that they're caused by a new mutation epigenetic inheritance though can lead to some interesting pedigrees with a parent of Origins what's important in who gets the disease for example a Ube 3A mutation passed down from the father is asymptomatic since that copy would be turned off anyway you might think that a deletion on chromosome 15 or maternal uniparental dysomy of chromosome 15 would also be asymptomatic but it turns out that there are important genes next to the Angelman syndrome region that are imprinted in the opposite way meaning only the paternally derived ones are expressed so in this case if those paternal genes are lost like with deletion or maternal uniparental dysomy then it results in a different disease called Prater Willy syndrome and this is the reason that this part of chromosome 15 is called the Prater Willy Angelman region in infancy Prada wooly Syndrome causes low muscle tone and poor feeding while later on causes overeating obesity low IQ and inadequate genital development infants and children that develop Angelman Syndrome have delayed development meaning that it might take them months or years longer than other children to achieve specific Milestones like sitting independently most children with Angelman syndrome never learn to speak and although most do learn how to walk they're often unsteady and tend to walk with arms flexed and hands pronated so that the Palms facing downward to the ground other common features include seizures difficulty with sleep a small head size a fair complexion and scoliosis children with Angelman syndrome are often happy excitable and have hand flapping movements but these are also common among children in general so they're only noteworthy when other symptoms are present there's no cure for Angelman syndrome so problems are addressed one by one for example communication boards can be used because of the absent speech all right as a quick recap Angelman syndrome is an imprinting disorder with the expression of Ube 3A and the maternal copy of chromosome 15 which is the only copy expressed in the brain is compromised causing severe intellectual disability seizures laughter and ataxia helping current and future clinicians Focus learn retain and Thrive learn more