A family with X-linked optic atrophy linked to the OPA2 locus Xp11.4-Xp11.2

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Am J Med Genet A. 2006 Sep 12

A family with X-linked optic atrophy linked to the OPA2 locus Xp11.4-

Xp11.2.

Katz BJ, Zhao Y, Warner JE, Tong Z, Yang Z, Zhang K.

Department of Ophthalmology and Visual Sciences, A Moran Eye

Center, University of Utah Health Sciences Center, Salt Lake City,

Utah.

Autosomal dominant optic atrophy (ADOA) is the most common inherited

optic atrophy. Clinical features of ADOA include a slowly progressive

bilateral loss of visual acuity, constriction of peripheral visual

fields, central scotomas, and color vision abnormalities. Although

ADOA is the most commonly inherited optic atrophy, autosomal

recessive, X-linked, mitochondrial, and sporadic forms have also been

reported.

Four families with X-linked optic atrophy (XLOA) were previously

described. One family was subsequently linked to Xp11.4-Xp11.2

(OPA2). This investigation studied one multi-generation family with

an apparently X-linked form of optic atrophy and compared their

clinical characteristics with those of the previously described

families, and determined whether this family was linked to the same

genetic locus.

Fifteen individuals in a three-generation Idaho family underwent

complete eye examination, color vision testing, automated perimetry,

and fundus photography. Polymorphic markers were used to genotype

each individual and to determine linkage. Visual acuities ranged from

20/30 to 20/100. All affected subjects had significant optic nerve

pallor. Obligate female carriers were clinically unaffected.

Preliminary linkage analysis (LOD score = 1.8) revealed that the

disease gene localized to the OPA2 locus on Xp11.4-Xp11.2. Four forms

of inherited optic neuropathy, ADOA, autosomal recessive optic

atrophy (Costeff Syndrome), Leber hereditary optic neuropathy, and

Charcot-Marie-Tooth disease with optic atrophy, are associated with

mitochondrial dysfunction.

Future identification of the XLOA gene will reveal whether this form

of optic atrophy is also associated with a mitochondrial defect.

Identification of the XLOA gene will advance our understanding of the

inherited optic neuropathies and perhaps suggest treatments for these

diseases. An improved understanding of inherited optic neuropathies

may in turn advance our understanding of acquired optic nerve

diseases, such as glaucoma and ischemic optic neuropathy.