Dominant optic atrophy, enorineural hearing lo, ptoi, and ophthalmoplegia: A yndrome caued by a miene mutation in OPA1

Purpoe To decribe the clinical feature of and identify the dieae-cauing mutation in a large Utah family egregating a dominantly inherited yndrome of optic atrophy, enorineural hearing lo, ptoi, and ophthalmoplegia. Deign Obervational cae erie. Method Thirty individual at rik for a yndrome of optic atrophy, enorineural hearing lo, ptoi, and ophthalmoplegia in a ingle family underwent clinical examination and venipuncture. Linkage analyi and mutation creening of the optic atrophy 1 gene (OPA1) were performed. Reult Eighteen individual demontrated characteritic of the yndrome. Genetic analyi identified a G→A ubtitution at nucleotide poition 1334 in exon 14 of OPA1 cauing an arginine-to-hitidine change (R445H) in all affected member of the family. Thi change egregated with the dieae phenotype in the tudy family with a LOD core of 7.02 at θ = 0 and wa not found in 200 normal control ubject. Analyi of an unrelated Belgian family with a imilar phenotype revealed the ame R445H mutation egregating with the dieae phenotype. Concluion Thi tudy decribe a mutation in OPA1 cauing a unique yndrome of optic atrophy, enorineural hearing lo, ptoi, and ophthalmoplegia. Thee reult expand the pectrum of human dieae aociated with mutation of OPA1 and indicate that ophthalmologit caring for patient with optic atrophy hould inquire about poible aociated hearing lo. Although OPA1 i a nuclear gene, the gene product localize to mitochondria, uggeting that mitochondrial dyfunction may be the final common pathway for many form of yndromic and nonyndromic optic atrophy, hearing lo, and external ophthalmoplegia.