ANGELMAN SYNDROME (AS)
UBE3A Sequencing
Also see: Angelman Syndrome - FISH Analysis and DNA Methylation Analysis 

Angelman syndrome is caused by maternal deletions of 15q11-q13, paternal uniparental disomy, imprinting defects, and by mutations in the UBE3A gene. UBE3A encodes the E6-AP ubiquitin ligase protein. This brain-specific imprinted gene demonstrates expression of the maternal allele in the brain, but biallelic expression in other tissues. Mutations in the UBE3A gene account for approximately 5% of all Angelman syndrome cases. Point mutations and small deletions and insertions have been identified in both familial and de novo cases. Diagnostic sequence analysis of the UBE3A coding region is being offered for Angelman syndrome patients who are negative for deletion, paternal UPD or imprinting defects as determined by normal results on the AS methylation testing.

Reasons for Referral:

  • Confirmation of diagnosis of Angelman syndrome.
  • Requires prior negative results on the AS methylation assay.

Testing Methodology:

PCR amplification of ten exons contained in the UBE3A gene coding region will performed on patient genomic DNA. Direct sequencing of amplification products is performed in both the forward and reverse directions using automated fluorescence dideoxy sequencing methods.

Specimen Requirements:

Blood: EDTA (purple-top) tubes: Adults: 14 cc; Child: 6 cc
Documentation of negative methylation test and requisition form required. Please contact the laboratory for specific requirements for prenatal testing.

Turnaround Time:

4 weeks

CPT Codes and Prices:

A 20% up-front payment is required for the index case before specimen can be processed.
Index: 83904x24, 83912, 83909x24, 83898, 83894, 83891
Known Familial Mutation: 83904x2, 83912, 83909x2, 83898, 83891, 83894

References:

1. Matsuura T, et al. (1997) Nat. Genet. 15: 74-77.
2. Fang P, et al. (1999) Hum. Mol. Genet. 8: 129-135.

Shipping Information

Forms:

 >> Gene Sequencing Requisition
 >> Prenatal Requisition

Test Codes:

Index: 6007
Known Familial Mutation: 6073
Prenatal (Known Familial Mutation Only): 6072