LEBER'S OPTIC NEUROPATHY (LHON) POINT MUTATIONS

Four Primary Mutations

MITOCHONDRIAL DNA ANALYSIS

Also known as: Hereditary Optic Neuroretinopathy, LHON, Leber's Disease, Leber's Optic Atrophy, Leber's Optic Neuropathy
Included in: Mitochondrial DNA Screen (Point Mutations and Deletions)
See also: 3525 - Autosomal Dominant Optic Atrophy 3 - OPA3 sequencing; 3465 - Optic Atrophy Type I - OPA1 sequencing

Leber’s optic neuropathy (LHON) is a maternally inherited late-onset optic atrophy. LHON usually presents with acute or subacute, painless loss of central visual acuity that occurs between 12 and 30 years of age. The typical opththalmoscopic features include circumpapillary telangiectatic microangiopathy and swelling of the nerve fiber layer around the optic disc. While most LHON patients manifest only optic atrophy, some patients present with additional or alternative clinical symptoms including pediatric-onset dystonia. Once visual loss has occurred, spontaneous recovery is uncommon but has been reported in a few patients. Most of the mutations responsible for LHON are homoplasmic missense mutations, although heteroplasmic mutations have also been reported. The penetrance of the disease is up to approximately 80% in males and much lower (about 8-30%) in females. There are three common primary mutations (sufficient by themselves to cause the disease); 11778G>A (ND4, R>H), 3460G>A (ND1, A>T), and 14484T>C (ND6, M>V), that account for more than 90% of the LHON cases. In addition, the 14459G>A (ND6, A>V) mutation has been reported in several families with variable phenotypic expression including dystonia, ataxia, hearing loss, and LHON.

Reasons for Referral:

To confirm the diagnosis of multisystemic mitochondrial DNA deletion syndrome.
Family history
Asymptomatic carrier testing if a specific mutation in the family is known

Testing Methodology:

The following point mutations are analyzed by multiplex PCR/ASO method: 11778G>A, 3460G>A, 14484T>C, and 14459G>A

Sensitivity:

Single deletion 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

Turnaround Time:

2 weeks

CPT Codes and Prices:

Index: 83896x15, 83893x15, 83901x2, 83912, 83891, 83900
Known Familial Mutation: 83904x4, 83898x2, 83912, 83891, 83894x2

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.
Wong LJC, Senadheera D. (1997) Direct detection of multiple point mutations in mitochondrial DNA Clinical Chemistry 43: 1857-1861.

Test Codes:

Index: 3025
Known Familial Mutation: 3026