AUTOSOMAL DOMINANT OPTIC ATROPHY 3

OPA3 Sequencing

Also known as: Autosomal Recessive Optic Atrophy-3
See also: 3465 - Optic Atrophy Type I - OPA1 sequencing; 3025 - Leber's Optic Neuropathy (LHON) Point Mutations

Hereditary optic atrophy is a heterogeneous group of genetic disorders. The most common forms of optic atrophy are autosomal dominant optic atrophy (ADOA, OMIM 165500) and Leber's hereditary optic neuropathy (LHON). ADOA, which generally starts in childhood, is characterized by a progressive decrease in visual acuity, blue-yellow dyschromatopsia, loss of sensitivity in the central visual field, and optic nerve pallor. OPA1 gene mutations are implicated in about 60–80% of the cases of ADOA.

OPA3 is responsible for the third form of hereditary optic atrophy, which is also known as autosomal dominant optic atrophy and cataract (ADOAC MIM 165300). More importantly, OPA3 gene mutations are implicated in autosomal recessive syndromic optic atrophy (OMIM 258501), also known as the Costeff syndrome (type III 3-methylglutaconic aciduria (MGA)) or the optic atrophy plus syndrome. It consists of early onset bilateral optic atrophy, later onset spasticity, extrapyramidal signs, and cognitive deficit. Increased urinary excretions of 3-methylglutaconic acid and elevated plasma 3-methylglutaric acid level are the hallmarks of Costeff syndrome.

OPA3 is located in the mitochondrial inner membrane and of unknown function. Northern blot analysis demonstrated a primary transcript of approximately 5.0 kb that was ubiquitously expressed, most prominently in skeletal muscle and kidney. The OPA3 gene contains 2 exons and maps to 19q13.2_3. There are two alternative splicing isoforms for OPA3: isoform A (180 amino acids) and isoform B (179 amino acids).

Reasons for Referral:

Confirmation of a clinical diagnosis
Carrier testing

Testing Methodology:

The exons and flanking intronic regions of the OPA3 gene are PCR amplified and sequenced in both forward and reverse directions.

Specimen Requirements:

Blood: EDTA (purple-top) tubes: Adult: 14 cc; Child: 6 cc; Infant: 2-3 cc.
Requisition form must accompany the specimen. To receive forms, additional information or specimen collection kits, please contact the laboratory.

Turnaround Time:

Index: 4 weeks
Known Familial Mutation: 2 weeks

CPT Codes and Prices:

Index: 83912, 83894, 83891, 83898x3, 83904x6, 83909x6
Known Familial Mutation: 83912, 83894, 83891, 83898, 83904x2, 83909x2

Shipping Information

Forms:

>> Gene Sequencing Requisition

References:

Chevrollier A, Guillet V, Loiseau D, et al.Hereditary optic neuropathies share a common mitochondrial coupling defect. Ann. Neurol. 2008 Jun; 63(6): 794-8.
Votruba M. Molecular genetic basis of primary inherited optic neuropathies. Eye. 2004 Nov; 18(11): 1126-32.
Reynier P, Amati-Bonneau P, Verny C, et al. OPA3 gene mutations responsible for autosomal dominant optic atrophy and cataract. J. Med. Genet. 2004 Sep; 41(9): e110.

Test Codes:

Index: 3525
Known Familial Mutation: 3526