Dominant Optic Atrophy, Deafness, Ptosis, Ophthalmoplegia, Dystaxia, and Myopathy

Treft, Robert L.; Sanborn, George E.; Carey, John C.; Swartz, Mano; Crisp, Darrell; Wester, Derin; Creel, Donnell J.

doi:10.1016/s0161-6420(84)34214-2

Cited by 33 publications

(15 citation statements)

References 28 publications

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“…Association of hearing deWcits with autosomal dominant optic atrophy (adOA) was described in several cases (Hoyt 1980;Treft et al 1984). Association of moderate bilateral loss of hearing thresholds with a speciWc mutation (R445H) in the OPA1 gene was recently discovered (Amati-Bonneau et al 2003, 2005Shimizu et al 2003;Payne et al 2004;Li et al 2005).…”

Section: Discussionmentioning

confidence: 99%

“…If they are present, they are usually minor or inconsistent. There are, however, several cases of optic atrophy associated with sensorineural hearing loss (Hoyt 1980;Treft et al 1984). It has been shown recently that the R445H mutation of OPA1, altering a highly conserved residue in the GTPase domain, is involved in adOA and moderate progressive hearing loss (adOAD) or in a more complex syndrome including adOA, hearing loss, ptosis and ophthalmoplegia (Amati-Bonneau et al 2003, 2005Shimizu et al 2003;Payne et al 2004;Li et al 2005).…”

Section: Introductionmentioning

confidence: 99%

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OPA1, the disease gene for optic atrophy type Kjer, is expressed in the inner ear

Bette

Zimmermann

Wissinger

et al. 2007

Histochem Cell Biol

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Autosomal dominant optic atrophy (adOA) is the most common form of hereditary optic neuropathy. The majority of cases are associated with mutations in the OPA1 gene. A few cases of adOA are known to be associated with moderate progressive hearing loss. To gain insight into the pathogenesis of this hearing loss, we performed expression analyses of OPA1 in the rat auditory and vestibular organ. In cochlear tissue, several splice variants of OPA1 were detected, which are also expressed in retinal tissue. OPA1 mRNA and protein was found in the hair cells and ganglion cells of the cochlea and vestibular organ. In ganglion cells, OPA1 mRNA and protein was already detectable at birth, whereas in the organ of Corti OPA1 mRNA and protein was up-regulated after birth and reached mature-like expression level during the onset of hearing. Comparison of an antibody directed to the mitochondrial marker protein HSP60 with antibodies directed to different amino acid stretches of OPA1 revealed a sub-cellular distribution of OPA1 in areas of significant density of mitochondria. The data suggest that defects in OPA1 cause hearing disorders due to a progressing metabolic disturbance of hair and ganglion cells in the inner ear.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

OPA1, the disease gene for optic atrophy type Kjer, is expressed in the inner ear

Bette

Zimmermann

Wissinger

et al. 2007

Histochem Cell Biol

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“…The extended haplotype was different from the two previously reported families, indicating that this is an independent mutation (data not shown). Treft et al [1984] and Meire et al [1985] reported a syndrome of optic atrophy, hearing loss, ptosis, and ophthalmoplegia with autosomal dominant inheritance in two unrelated families. When these two families were subsequently studied, the syndrome was found to result from an R445H mutation in the OPA1 gene [Payne et al, 2004].…”

Section: Linkage Analysis and Mutation Detectionmentioning

confidence: 99%

“…In 1984, Treft et al described an autosomal dominant disorder in 23 members of a large Utah family in which affected individuals exhibited progressive optic atrophy, sensorineural hearing loss, ptosis, ophthalmoplegia, ataxia, and a nonspecific myopathy [Treft et al, 1984]. The following year, Meire et al reported an unrelated family from Belgium with a similar phenotype [Meire et al, 1985].…”

Section: Introductionmentioning

confidence: 99%

Optic atrophy and sensorineural hearing loss in a family caused by an R445H OPA1 mutation

Kosmorsky

Zhang

et al. 2005

American J of Med Genetics Pt A

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Autosomal dominant optic atrophy (ADOA) is the most common form of inherited optic atrophy. Four genetic loci have been associated with ADOA: OPA1, OPA2, OPA3, and OPA4. Out of these four loci, only one gene has been identified, OPA1. We previously described a unique syndrome of optic atrophy, sensorineural hearing loss, ptosis, and ophthalmoplegia in two unrelated families associated with an R445H mutation in OPA1. The R445H mutation is the only OPA1 mutation that has been associated with this syndrome. In this manuscript, we clinically characterize an unrelated family with four members affected by optic atrophy and hearing loss without extraocular motility abnormalities or ptosis. This family also harbors the R445H mutation. These cases help illustrate the intra- and inter-family variability in phenotype associated with this mutation. As we continue to learn more about OPA1 and the function of its protein product, we will begin to understand the pathophysiology of optic atrophy. This understanding will ultimately lead to novel treatments directed toward preventing the visual loss and disability associated with this inherited disease.

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“…Phenotype-genotype studies of optic atrophies have led to the identification of severe phenotypes, the so-called "ADOA plus" phenotypes, which associate OPA1 mutations with syndromic forms of optic atrophy including sensorineural deafness (ADOAD; MIM# 125250) Shimizu et al, 2003), and ptosis and myopathy (Amati-Bonneau et al, 2007;Hudson et al, 2008;Meire et al, 1985;Payne et al, 2004;Treft et al, 1984).…”

Section: Introductionmentioning

confidence: 99%

Molecular screening of 980 cases of suspected hereditary optic neuropathy with a report on 77 novelOPA1mutations

et al. 2009

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ABSTRACT:We report the results of molecular screening in 980 patients carried out as part of their work-up for suspected hereditary optic neuropathies. All the patients were investigated for Leber's hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (ADOA), by searching for the ten primary LHON-causing mtDNA mutations and examining the entire coding sequences of the OPA1 and OPA3 genes, the two genes currently identified in ADOA. Molecular defects were identified in 440 patients (45% of screened patients). Among these, 295 patients (67%) had OFFICIAL JOURNAL www.hgvs.org E693 Molecular Screening of 980 Cases of Suspected Hereditary Optic Neuropathyan OPA1 mutation, 131 patients (30%) had an mtDNA mutation, and 14 patients (3%), belonging to three unrelated families, had an OPA3 mutation. Interestingly, OPA1 mutations were found in 157 (40%) of the 392 apparently sporadic cases of optic atrophy. The eOPA1 locus-specific database now contains a total of 204 OPA1 mutations, including 77 novel OPA1 mutations reported here. The statistical analysis of this large set of mutations has led us to propose a diagnostic strategy that should help with the molecular work-up of optic neuropathies. Our results highlight the importance of investigating LHON-causing mtDNA mutations as well as OPA1 and OPA3 mutations in cases of suspected hereditary optic neuropathy, even in absence of a family history of the disease.

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Dominant Optic Atrophy, Deafness, Ptosis, Ophthalmoplegia, Dystaxia, and Myopathy

Cited by 33 publications

References 28 publications

OPA1, the disease gene for optic atrophy type Kjer, is expressed in the inner ear

OPA1, the disease gene for optic atrophy type Kjer, is expressed in the inner ear

Optic atrophy and sensorineural hearing loss in a family caused by an R445H OPA1 mutation

Molecular screening of 980 cases of suspected hereditary optic neuropathy with a report on 77 novelOPA1mutations

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