Prader Willi/Angelman Syndrome – Methylation Sensitive HRM

Diagnostic Use

Prader-Willi Syndrome (PWS) (OMIM 176270) is characterised by severe hypotonia and feeding difficulties in early infancy, followed in early childhood by excessive eating, morbid obesity, delayed motor milestones, language development and cognitive impairment. Individuals also have hypogonadism, short stature, characteristic facial features and a distinctive behavioural phenotype (with temper tantrums, stubbornness, manipulative behaviour, and obsessive-compulsive characteristics).
Angelman Syndrome (AS) (OMIM 105830) is characterised by severe developmental delay or mental retardation, severe speech impairment, gait ataxia and/or tremulousness of the limbs, and a unique behaviour with an inappropriate happy demeanour that includes frequent laughing, smiling and excitability. Microcephaly and seizures are also common. The unique clinical features of AS do not become manifest until after one year of age, although developmental delay can sometimes be identified from 6 months.
These syndromes are genomic imprinting disorders associated with differentially methylated genes on chromosome 15q11.2-q13. PWS is caused by the loss of the paternal contribution of imprinted genes in 15q11.2-q13 region (gene/s unknown) and AS is caused by the loss of the maternal contribution of imprinted genes (UBE3A) in the same region.

Department

Genetics - Molecular Pathology

Delphic Registration Code

MOLP

Constituent Tests

• Genomic DNA Extraction

Synonyms

AS
PWS

Turnaround Time

4 weeks

Test Code

7087

Specimen Type

• Whole Blood

Specimen Requirements

Tube/Container Type:

Preferred

• EDTA (Lavender Cap)

Preferred Sample Volume (ml)

4.0

No of Samples Required

1

Paediatric Specimen Requirements

Tube/Container Type:

Preferred

• EDTA (Lavender Cap)

Preferred Sample Volume (ml)

1.0

Minimum Sample Volume (ml)

0.5

Pre-testing Requirements

It may be useful to discuss this testing with a Clinical Geneticist prior to requesting this test. Phone Genetic Health NZ.

Additional Specimen Information

This genetic test needs nucleated cells. Please don’t centrifuge or freeze the EDTA blood tube.
If storing blood tube prior to delivery please refrigerate at 4 degrees (transport still at ambient temperature).

Aliquot Instructions

Sample Type

• Whole Blood

Transport to Lab

Ambient (8 - 24 degrees Celsius)

Additional Referral/Aliquot Information

Please don’t centrifuge or freeze the EDTA blood tube.
If storing blood tube prior to delivery please refrigerate at 4 degrees (transport still at ambient temperature).

Test Method

PW/AS is detected by a molecular genetic method called Methylation Sensitive HRM. Please refer to our testing flow chart. A microarray should also be performed as microarray testing detects all currently known microdeletion syndromes in one assay and can also determine the exact region deleted. An array is especially recommended when the diagnosis of PW/AS is not certain, or in very young paediatric cases. Microarray testing will detect ~70% of PWS or AS, ie. all cases caused by chromosome 15 deletion and some cases of UPD(15).

Methylation specific PCR can be performed to confirm a diagnosis as almost 100% of PWS positive individuals and 70-80% of AS positive individuals can be detected by this method. Depending on the result, further analysis will be performed to detect the underlying cause.

Contact Canterbury Health Laboratories on +64 3 364 0484 or email LabInfo@cdhb.health.nz

Genomic DNA must be extracted from the specimen prior to testing. This incurs an additional charge (see GDNA). Laboratories may prefer to submit DNA for testing. Please provide a minimum of 5 micrograms of DNA at 20 nanograms / microlitre.

Resources

• PWS-AS Flowchart (140 KB)

Contact Information

Enquiry Form

Contact Information

Enquiry Form