Childhood Absence Epilepsy: GABRB3 Gene Sequencing

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Condition Description

Childhood absence epilepsy (CAE), which is a common idiopathic generalized epilepsy, accounts for 10-20% of all epilepsy in children under the age of 16 years.  Absence seizures are characterized by a brief loss of consciousness lasting between three and ten seconds and can occur up to 200 times a day.  Tanaka et al. (2008) identified three missense mutations in the GABRB3 gene (15q11.2-q12) in four out of 48 families (8%) with remitting CAE. 

For patients with suspected childhood absence epilepsy, sequence analysis is recommended as the first step in mutation identification. For patients in whom mutations are not identified by full gene sequencing, deletion/duplication analysis is appropriate.

References:

Genes (1)

Indications

This test is indicated for:
  • Confirmation of a clinical diagnosis of childhood absence epilepsy.
  • Carrier testing in adults with a family history of childhood absence epilepsy.

Methodology

PCR amplification of 9 exons contained in the GABRB3 gene is performed on the patient's genomic DNA. Direct sequencing of amplification products is performed in both forward and reverse directions, using automated fluorescence dideoxy sequencing methods. The patient's gene sequences are then compared to a normal reference sequence. Sequence variations are classified as mutations, benign variants unrelated to disease, or variations of unknown clinical significance. Variants of unknown clinical significance may require further studies of the patient and/or family members. This assay does not interrogate the promoter region, deep intronic regions, or other regulatory elements, and does not detect large deletions.

Detection

Clinical Sensitivity: Tanaka et al. (2008) identified missense mutations in the GABRB3 gene in 4 out of 48 families (8%) with remitting CAE.  Mutations in the promoter region, some mutations in the introns and other regulatory element mutations cannot be detected by this analysis. Large deletions will not be detected by this analysis. Results of molecular analysis should be interpreted in the context of the patient's clinical and/or biochemical phenotype.

Analytical Sensitivity: ~99%

Specimen Requirements

Submit only 1 of the following specimen types

Preferred specimen type: Whole Blood

Type: Whole Blood

Specimen Requirements:

In EDTA (purple top) or ACD (yellow top) tube:
Infants (<2 years): 2-3 ml
Children (>2 years): 3-5 ml
Older Children & Adults: 5-10 ml

Specimen Collection and Shipping: Refrigerate until time of shipment. Ship sample within 5 days of collection at room temperature with overnight delivery.

Type: Saliva

Specimen Requirements:

OrageneTM Saliva Collection kit (available through EGL) used according to manufacturer instructions.

Specimen Collection and Shipping: Store sample at room temperature. Ship sample within 5 days of collection at room temperature with overnight delivery.

  • Deletion/duplication analysis of the GABRB3 gene by CGH array is available for those individuals in whom sequence analysis is negative.
  • Custom diagnostic mutation analysis (KM) is available to family members if mutations are identified by targeted mutation testing or sequencing analysis.
  • Prenatal testing is available only for known familial mutations to individuals who are confirmed carriers of mutations. Please contact the laboratory genetic counselor to discuss appropriate testing prior to collecting a prenatal specimen.

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