MITOCHONDRIAL DNA SCREENING PANEL (POINT MUTATIONS AND DELETIONS)

MITOCHONDRIAL DNA ANALYSIS

Mitochondrial DNA disorders are a group of maternally inherited clinically and genetically heterogeneous multisystemic disorders. The mitochondrial DNA mutation screen includes the analysis for the point mutations or large DNA deletions in the mitochondrial genome that cause the mitochondrial syndromes listed below.

Disorders	Mutations	Gene
MELAS (mitochondrial encephalopathy, lactic acidosis, stroke-like episodes)	3243A>G, 3271T>C	tRNA^Leu(UUR)
MERRF (myoclonic epilepsy and ragged red fibers)	8344A>G, 8356T>C	tRNA^lys
NARP (neuropathy, ataxia, retinitis pigmentosa), Leigh syndrome	8993T>G, 8993T>C	ATPase-6
Cardiomyopathy	8363G>A	tRNA^lys
Leigh, Leigh-like disease, MELAS	13513G>A, 13514A>G	ND5
LHON (Leber’s Optic Neuropathy)	11778G>A, 3460G>A, 14459G>A, 14484T>C	ND4, ND1, ND6
Kearns-Sayre syndrome	large deletions	tRNAs+mRNA
CPEO (chronic progressive external ophthalmoplegia)	large deletions	tRNAs+mRNA
Pearson marrow/pancreas syndrome	large deletions	tRNAs+mRNA
Maternally inherited diabetes/hearing loss	large deletions	tRNAs+mRNA
Mitochondrial DNA Deletion Syndrome

Reasons for Referral:

Multisystemic disorders involving neuromuscular, neurosensory, central nervous system, cardiac, renal, hepatic, GI, immune, and endocrine systems
Family history of mitochondrial disorders
Matrilineal family members with known mitochondrial DNA mutations
Confirmation of mitochondrial disease

Testing Methodology:

Point mutations are detected by a multiplex PCR/ASO method and quantified by real time ARMS quantitative PCR. Large deletions are detected by Southern analysis.

Sensitivity:

Heteroplasmic point mutations at as low as 1% can be detected. Single deletions of larger than 500 bp at greater than 10% heteroplasmy can be detected by Southern analysis.

Specimen Requirements:

Blood: EDTA (purple-top) tubes: Adult: 14 cc; Child: 6 cc; Infant: 2-3 cc. Patients with suspected Kearns-Sayre syndrome should submit muscle specimen for analysis.
Tissue: Skeletal muscle (Preferred). 50 mg for muscle DNA analysis, 150mg for muscle ETC analysis, >200mg if additional tests are requested. Heart, brain, liver, kidney or fibroblast cultures also accepted. 50 mg of heart, brain, liver, kidney or fibroblast for DNA analysis. Tissues such as liver and kidney should be snap-frozen at collection, stored at -70, and shipped on 3-5 lbs of dry ice.

Turnaround Time:

3 weeks

CPT Codes and Prices:

83896x20, 83894x2, 83893x18, 83892x2, 83912, 83901, 83897x2, 83891, 83900

Shipping Information

Forms:

>> Mitochondrial Requisition - Mitochondrial Diagnostic Checklist is included

References:

Wong LJC, Boles R. (2005) Mitochondrial DNA in clinical laboratory diagnostics. Review Article, Clinica Chimica Acta 354: 1-20.
Shanske S, Wong LJC. (2004) Molecular analysis for mitochondrial DNA disorders. Mitochondrion 4: 403-415.
Liang MH, Wong LJC. (1998) Yield of mtDNA mutation analysis in 2000 patients. Am. J. Med. Genet. 77: 395-400.

Test Codes:

3000