Getting an Accurate Diagnoses​

Genetic Health Service NZ provides genetic diagnostic and genetic counselling services, operating fourteen clinics throughout the country. They also provide assistance in managing genetic conditions, expert advice on genetic diseases and education on genetics.

 

How to test for Angelman Syndrome​

• Genetic testing 101 (FAST)

• Testing & Diagnoses of Angelman syndrome (ASF)​

AS diagnosis requires taking a blood sample from your child for genetic studies and it determines parental DNA pattern, missing chromosomes, and gene mutation. Parental DNA pattern, known as a DNA methylation test, screens for three out of four mechanisms that cause the syndrome. A fluorescence in situ hybridization test or a comparative genomic hybridization test can determine missing chromosomes. Sometimes, Angelman may occur when a person's maternal copy of the UBE3A gene is active, but mutated and that decides whether or not the child has the syndrome.

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A breakdown of the main AS genotypes​

Angelman Syndrome is caused by a severe reduction of expression of a single gene UBE3a in the brain. (UBE3A is a ubiquitin ligase whose function and targets relevant to AS are still unknown).

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1. Deletion +, or 15q11.2-q13 deletions (68% of cases) – the majority of AS cases are caused by deletions on the maternal copy of Chromosome 15. Due to genomic imprinting, only the maternal copy of UBE3A is expressed in the brain. The deletion removes the normal expression of this gene in AS individuals.

2. UBE3A mutations (11% of cases) – In these individuals, mutations in the UBE3A gene either prevent its expression or function. Thus these individuals do not have the appropriate levels of functional UBE3A in the brain.

3. Uniparental disomy (UPD; 7% of cases) – in UPD, the individual has two copies of paternal Chromosome 15. Because UBE3A is not expressed from the paternal copy, these individuals lack normal levels of UBE3A in the brain.

4. Imprinting defect (3% of cases) – These individuals may have a deletion of the imprinting center an Chromosome 15, but could also be caused by loss of imprinting information during the mother’s oogenesis. Loss of imprinting will prevent expression of the maternal UBE3A gene in the brain.

5. Clinical/other (11%) – In these individuals, all testing for Angelman Syndrome is normal, but they still meet the diagnostic criteria for AS. These individuals may have as yet unrecognized mutations that affect UBE3A or genomic imprinting on Chromosome 15.

 

Whole Exome Sequencing​

Further testing: The purpose of whole exome sequencing is to find a genetic cause of your/your child’s symptoms. Most people who have WES have already had some genetic testing. WES is one of the most extensive genetic tests available. Because WES looks at more genes than most genetic tests, it may find a genetic cause, even if previous genetic testing did not.

Read more on Whole Exome Sequencing

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Prenatal Genetic Diagnosis for Angelman Syndrome

Read more here