Angelman Syndrome Methylation Analysis

Clinical Use

Use

The Angelman Syndrome Methylation Analysis is crucial for assessing parent-specific imprinting within the Prader-Willi/Angelman critical region on chromosome 15, enabling the detection of over 99% of individuals with Prader-Willi syndrome and 80% of those with Angelman syndrome. Accurate findings in this assay are essential not just for diagnosis but for useful clinical management. Individuals with positive results are encouraged to undergo complementary testing, including Chromosomal Microarray - High Resolution (test code 8655) and/or uniparental disomy studies for proper etiology assessment. Moreover, this assay is capable of identifying cases of Prader-Willi syndrome, thus providing comprehensive insight into the relevant genetic landscape.

Special Instructions

Indications for Testing: Patients with a clinical or suspected diagnosis of Prader-Willi Syndrome or Angelman syndrome, including hypotonia, global developmental delay, poor feeding, hypogonadism, gait ataxia, microcephaly, seizures, and/or a happy demeanor. This disease follows non-Mendelian inheritance. Angelman syndrome is an imprinting disorder caused by absence of the maternally derived 15q11.2-q13 chromosome region, with most patients (80-84%) exhibiting abnormal DNA methylation pattern.

Limitations

While Methylation analysis serves as a useful diagnostic tool, it cannot differentiate between the causes of Angelman syndrome that result from maternal 15q11-13 deletion, paternal uniparental disomy, or an imprinting defect. Due to the complex nature of genetic variations and allelic imprinting, patients may require further investigations. For instance, individuals presenting normal methylation results still have a 5-8% chance of carrying a mutation in the UBE3A gene, while another 10-15% remain undiagnosed regarding their molecular etiology. Hence, follow-up tests are recommended for comprehensive genetic evaluation.

Test Details

New York Approved

Methodology

Other

Biomarkers

2 components

Primary ComponentSouthern Blot Analysis

Result Turnaround Time

21 days

Specimen

Tissue (Fresh)

Volume

5 cubic millimeters

Minimum Volume

5 cubic millimeters

Container

sterile container with RPMI media

Collection Instructions

Collect skin from a central location (e.g., buttock or upper thigh).

Storage Instructions

Ship at ambient temperature (18–25°C). Protect from excessive heat and ship in a cooled container during summer months. Sample must arrive within 72 hours.