What Can Be Learned From This Test
The diagnosis of LBSL is based on characteristic abnormalities observed on brain and spinal cord MRI and the identification of two alleles with mutations in DARS2. Finding two disease-causing mutations in DARS2 confirms the diagnosis of LBSL. However, absence of DARS2 mutations does not exclude the diagnosis when the clinical and MRI findings are characteristic, especially if all major diagnostic criteria and at least one supportive criterion are met.
Testing can be performed in tiers, moving to the next tier only if the preceding test is negative. Full gene sequencing can also be performed. The following strategy is suggested:
- Tier 1 sequencing of exons 3 , 5, and adjacent intronic regions of DARS2, which covers the three most common pathogenic variants:
- c.228-21_-20delTTinsC (rs367543010)
- c.455G>T (rs121918208)
- c.492+2T>C (rs14243333)
- Tier 2 sequencing of the remaining exons and intronic boundaries of DARS2
This will detect point mutations, small deletions, and small insertions. It will not detect a partial or whole gene deletion or duplication.
Draw 2ml–4ml of blood in EDTA/purple-top tube (minimum of 1ml–2ml for infants).
Turnaround time: 10-14 days per tier
CPT Codes and Cost
Full Gene Sequencing
Known Variant Testing