Dominant optic nerve atrophy with progressive hearing loss and chronic progressive external ophthalmoplegia (CPEO)

Meire, Françoise; Laey, J. J. De; Bie, Sylvia De; Staey, M. Van; Matton, M. Th.

doi:10.3109/13816818509007861

Cited by 34 publications

(15 citation statements)

References 6 publications

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“…AU = Austria; BE = Belgium; BR = Brazil; CN = China; DE = Germany; ES = Spain; FI = Finland; FR = France; IT = Italy; NO = Norway; UK = United Kingdom; US = USA; AA = amino acid; FHx = family history; HSP = hereditary spastic paraplegia; MS = multiple sclerosis-like illness; CAPOS = cerebellar ataxia, areflexia, pes cavus, optic atrophy and sensorineural hearing loss; CC = coiled-coil domain; GE = GTPase effector domain; PEO = progressive external ophthalmoplegia. a Age of death. b De novo OPA1 mutation. c In-frame skipping of exon 12 (p.T381-N404del).BE-1: (Meire et al , 1985; Payne et al , 2004); CN-1: (Li et al , 2005); CN-2: (Ke et al , 2006); CN-3: (Chen et al , 2007); ES-1: (Amati-Bonneau et al , 2005); FI-1: (Puomila et al , 2005); FR-6, FR-7, FR-8:(Amati-Bonneau et al , 2005); FR-9, FR-10: (Amati-Bonneau et al , 2008); IT-4: (Amati-Bonneau et al , 2008; Liguori et al , 2008); IT-5: (Amati-Bonneau et al , 2008); IT-6: (Spinazzi et al , 2008); IT-7: (Ferraris et al , 2008); UK-11: (Hudson et al , 2008); UK-12, UK-13, UK-14: (Stewart et al , 2008); US-1: (Payne et al , 2004); US-2: (Milone et al , 2009). …”

Section: Resultsmentioning

confidence: 99%

Multi-system neurological disease is common in patients with OPA1 mutations

Yu‐Wai‐Man

Griffiths

Gorman

et al. 2010

Brain

393

389

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Additional neurological features have recently been described in seven families transmitting pathogenic mutations in OPA1, the most common cause of autosomal dominant optic atrophy. However, the frequency of these syndromal ‘dominant optic atrophy plus’ variants and the extent of neurological involvement have not been established. In this large multi-centre study of 104 patients from 45 independent families, including 60 new cases, we show that extra-ocular neurological complications are common in OPA1 disease, and affect up to 20% of all mutational carriers. Bilateral sensorineural deafness beginning in late childhood and early adulthood was a prominent manifestation, followed by a combination of ataxia, myopathy, peripheral neuropathy and progressive external ophthalmoplegia from the third decade of life onwards. We also identified novel clinical presentations with spastic paraparesis mimicking hereditary spastic paraplegia, and a multiple sclerosis-like illness. In contrast to initial reports, multi-system neurological disease was associated with all mutational subtypes, although there was an increased risk with missense mutations [odds ratio = 3.06, 95% confidence interval = 1.44–6.49; P = 0.0027], and mutations located within the guanosine triphosphate-ase region (odds ratio = 2.29, 95% confidence interval = 1.08–4.82; P = 0.0271). Histochemical and molecular characterization of skeletal muscle biopsies revealed the presence of cytochrome c oxidase-deficient fibres and multiple mitochondrial DNA deletions in the majority of patients harbouring OPA1 mutations, even in those with isolated optic nerve involvement. However, the cytochrome c oxidase-deficient load was over four times higher in the dominant optic atrophy + group compared to the pure optic neuropathy group, implicating a causal role for these secondary mitochondrial DNA defects in disease pathophysiology. Individuals with dominant optic atrophy plus phenotypes also had significantly worse visual outcomes, and careful surveillance is therefore mandatory to optimize the detection and management of neurological disability in a group of patients who already have significant visual impairment.

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Section: Resultsmentioning

confidence: 99%

Multi-system neurological disease is common in patients with OPA1 mutations

Yu‐Wai‐Man

Griffiths

Gorman

et al. 2010

Brain

393

389

View full text Add to dashboard Cite

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“…The following year, Meire et al reported an unrelated family from Belgium with a similar phenotype [Meire et al, 1985]. We subsequently identified an R445H OPA1 mutation in both the Utah family and the family from Belgium [Payne et al, 2004].…”

Section: Introductionmentioning

confidence: 84%

“…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%

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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“…5 ADOA associated with hearing impairment not linked to OPA1 has been described in several instances. [9][10][11][12][13][14][15] One specific missense mutation, R445H, in OPA1 has been identified in four sporadic/familial cases with dual sensory impairment, and furthermore, in two families with ptosis, ophthalmoplegia, and movement disorders. 16 Autosomal recessive WS is characterised by juvenile onset diabetes mellitus and optic atrophy, with 60% of the patients showing various degrees of hearing impairment by 20 years of age, 17 and frequently endocrinological, psychiatric, urological, and neurological symptoms.…”

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confidence: 99%