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Paediatric Laboratory Medicine

Angelman Syndrome: UPD 15 Analysis

Clinical Significance

Angelman syndrome (AS) is characterized by severe developmental delay or mental retardation, severe speech impairment, gait ataxia and/or tremors in the limbs. Microcephaly and seizures are common. Affected individuals also display characteristic demeanor that includes inappropriate laughing, smiling, and excitability.

There are a number of genetic changes that cause AS, although each produces a similar clinical phenotype. Approximately 70% of cases are the result of a deletion in the maternally contributed chromosome 15q11-q13 region. Approximately 5% of cases have received two copies of chromosome 15 from their father and none from their mother: paternal uniparental disomy (patUPD). Like the deletion patients, paternal UPD patients are deficient for maternally derived genes in the AS critical region. Approximately 5% of patients have an 'imprinting mutation' which alters the normal expression of maternal genes in the AS critical region. Approximately 20% of clinically diagnosed AS patients have genetic alterations other than deletion, UPD or imprinting mutations. These mutations are not detected by methodology currently in place in the Molecular Genetics Laboratory, and samples may be referred to a research lab for further investigation.

DNA in the AS critical region is methylated. If the normal expression of genes in the critical region is altered due to deletion, UPD or imprinting mutations, the methylation pattern is also changed. Testing the methylation status of genes within the critical region therefore allows these genetic alterations to be detected. For molecular analysis, the methylation status of the gene SNRPN within the AS critical region is measured. Abnormal methylation of the maternally derived gene is diagnostic of Angelman syndrome.

Test Name

Angelman Syndrome: UPD 15 Analysis

Alternate Name/ Synonym

  • Happy Puppet Syndrome

Test Code

ANGEL

Division

Molecular Genetics

Method

UPD15 studies via STR (short tandem repeat) analysis

External Proficiency Testing

CAP

Turn Around Time

2 weeks (Prenatal samples), 2-3 weeks (Pregnancy/Urgent samples), 4-6 weeks (Routine)

Disease/Condition

Angelman Syndrome

Specimen Type

Blood; extracted DNA is not accepted for Angelman Syndrome: Methylation and Copy Number Analysis.

For details about specimen requirements, please refer to: Specimen Types & Requirements (PDF).

Minimum Specimen Requirements

5-10 mL EDTA or ACD, 0.5 mL EDTA (neonate); minimum 10 ug in 100 uL low TE (pH8.0)

Storage/Transportation

Room Temperature

Special Requirements

Special Instructions for Genome Diagnostics Samples

If sample shipment  >48 hours, ship on ice.

Approval is not required

CPT Codes

81402

Shipping and Contact Information

The Hospital for Sick Children
Rapid Response Laboratory
170 Elizabeth Street, Room 3642
Toronto, ON
M5G 2G3
Canada
Phone: 416-813-7200
Phone: 1-855-381-3212

Interpretation

Interpretation is provided in report

Information Sheet: Angelman Syndrome