Mutations in the MTTL1 mitochondrial gene (tRNA-Leu) have been identified in patients with MELAS. Mutations in MTTL1 can result in impaired mitochondrial respiratory chain complex I and cytochrome C oxidase activity. Reduction in mitochondrial respiratory chain function reduces that amount of ATP produced by the mitochondria.
The most common mutation in MTTL1, present in over 80% of patients with typical clinical findings of MELAS, is a 3243A>G transition in MTTL1. The MTTL1 mutations 3,271 T>C, 3,252 A>G, 3,291 T>C, and 3,260 A>G account for an additional 15-20% of all MELAS mutations. Other rare mutations in the MTTL1 gene have also been observed. Mitochondrial mutations outside the MTTL1 gene have been described in rare cases. Mutations associated with MELAS may be heteroplasmic with the degree of heteroplasmy varying in different tissues. Based on clinical presentation, either a blood or a tissue sample (muscle biopsy) may be used.
- Patients with a confirmed or suspected diagnosis of MELAS.
- Family members of an affected patient who are at risk for MELAS.
Detection and Reference Range
This assay will detect over 90% of mitochondrial mutations associated with MELAS. The 3243A>G mutation can be detected at approximately 10% heteroplasmy. All other mutations can be detected at approximately 15-20% heteroplasmy. Mutations outside the MTTL1 gene will not be detected.
Submit only 1 of the following specimen types
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: Muscle Biopsy
Specimen Requirements:1-2 mm in length or > 100 mg is acceptable.
Flash freeze sample upon collection using liquid nitrogen. If storage is required, store sample at -80o C or colder.
Specimen Collection and Shipping: Ship frozen sample on dry ice with overnight delivery.
- MERRF (QH) Testing may be indicated for patients who also show progressive external ophthalmaloplegia and ragged red fibers on muscle biopsy
- KSS/CPEO (QB) Testing may be indicated for patients who also show progressive external ophthalmaloplegia
- Myotonic Dystrophy (MD) may be indicated for patients who show muscle weakness