OPA1 R445H mutation in optic atrophy associated with sensorineural deafness

Amati‐Bonneau, Patrizia; Guichet, Agnès; Olichon, Aurélien; Chevrollier, Arnaud; Viala, F.; Miot, Stéphanie; Ayuso, Carmen; Odent, Sylvie; Arrouet, Catherine; Verny, Christophe; Calmels, M.; Simard, Gilles; Bélenguer, Pascale; Wang, Jing; Puel, Jean–Luc; Hamel, Christian; Malthièry, Yves; Bonneau, Dominique; Lenaers, Guy; Reynier, Pascal

doi:10.1002/ana.20681

Cited by 151 publications

(109 citation statements)

References 20 publications

(25 reference statements)

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“…The involvement of optic nerves as well as the post-lingual onset is inconsistent with mutations of both otoferlin (Rodriguez-Ballesteros et al, 2003) and pejvakin genes (Delmaghani et al, 2006). Mutations affecting mitochondrial functions of both optic and auditory nerves are candidate etiologies in these patients (Ceranić and Luxon, 2004;Amati-Bonneau et al, 2005).…”

Section: Adaptation Of Ecochg Potentials In Anmentioning

confidence: 99%

Neural and receptor cochlear potentials obtained by transtympanic electrocochleography in auditory neuropathy

Santarelli

Starr

Michalewski

et al. 2008

Clinical Neurophysiology

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Objective: Transtympanic electrocochleography (ECochG) was recorded bilaterally in children and adults with auditory neuropathy (AN) to evaluate receptor and neural generators. Methods: Test stimuli were clicks from 60 to 120 dB p.e. SPL. Measures obtained from eight AN subjects were compared to 16 normally hearing children. Results: Receptor cochlear microphonics (CMs) in AN were of normal or enhanced amplitude. Neural compound action potentials (CAPs) and receptor summating potentials (SPs) were identified in five AN ears. ECochG potentials in those ears without CAPs were of negative polarity and of normal or prolonged duration. We used adaptation to rapid stimulus rates to distinguish whether the generators of the negative potentials were of neural or receptor origin. Adaptation in controls resulted in amplitude reduction of CAP twice that of SP without affecting the duration of ECochG potentials. In seven AN ears without CAP and with prolonged negative potential, adaptation was accompanied by reduction of both amplitude and duration of the negative potential to control values consistent with neural generation. In four ears without CAP and with normal duration potentials, adaptation was without effect consistent with receptor generation. In five AN ears with CAP, there was reduction in amplitude of CAP and SP as controls but with a significant decrease in response duration. Conclusions: Three patterns of cochlear potentials were identified in AN: (1) presence of receptor SP without CAP consistent with presynaptic disorder of inner hair cells; (2) presence of both SP and CAP consistent with post-synaptic disorder of proximal auditory nerve; (3) presence of prolonged neural potentials without a CAP consistent with post-synaptic disorder of nerve terminals. Significance: Cochlear potential measures may identify pre-and post-synaptic disorders of inner hair cells and auditory nerves in AN.

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Section: Adaptation Of Ecochg Potentials In Anmentioning

confidence: 99%

Neural and receptor cochlear potentials obtained by transtympanic electrocochleography in auditory neuropathy

Santarelli

Starr

Michalewski

et al. 2008

Clinical Neurophysiology

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“…The gene encoding for Opa1 is composed of 30 exons, and at least eight mRNA isoforms arising from alternative splicing and with tissue-specific expression have been identified (Delettre et al, 2001). A total of 83 family-specific mutations have been associated with ADOA so far, and their number seems to be growing (Alexander et al, 2000;Delettre et al, 2000Delettre et al, , 2001Delettre et al, , 2002Pesch et al, 2001;Thiselton et al, 2001Thiselton et al, , 2002Toomes et al, 2001;Marchbank et al, 2002;Shimizu et al, 2002;Amati-Bonneau et al, 2005;Ferre et al, 2005). About half of the mutations associated with the disease are located within the GTPase domain, suggesting that pathogenesis is related to loss of function of the protein and haploinsufficiency in patients with mutation on a single allele (Ferre et al, 2005).…”

Section: Fusionmentioning

confidence: 99%

The many shapes of mitochondrial death

2006

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“…Nevertheless, the protein is expressed in all examined human tissues, explaining the accidental development of the so-called 'ADOA +' forms characterized by the association of the blindness with various neuromuscular disorders [17][18][19] or hearing loss [20,21]. The vulnerability of retinal ganglion cells and that of spiral ganglion cells in the inner ear [22] has been attributed to the impairment of ATP production as observed in fibroblasts [23,24] or skeletal muscle [25].…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial Ca2+ uptake correlates with the severity of the symptoms in autosomal dominant optic atrophy

Fülöp¹,

Rajki²,

Maka³

et al. 2015

Cell Calcium

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The most frequent form of hereditary blindness, Autosomal Dominant Optic Atrophy (ADOA) is caused by the mutation of the mitochondrial protein Opa1 and the ensuing degeneration of retinal ganglion cells. Previously we found that knockdown of OPA1 enhanced mitochondrial Ca 2+ uptake (Fülöp et al.,PLoS One 2011). Therefore we studied mitochondrial Ca 2+ metabolism in fibroblasts obtained from members of an ADOA family. Gene sequencing revealed heterozygosity for a splice site mutation (c. 984+1G>A) in intron 9 of the OPA1 gene. ADOA cells showed a higher rate of apoptosis than control cells and their mitochondria displayed increased fragmentation when forced to oxidative metabolism. The ophthalmological parameters critical fusion frequency and ganglion cell -inner plexiform layer thickness were inversely correlated to the evoked mitochondrial Ca 2+ signals. The present data indicate that enhanced mitochondrial Ca 2+ uptake is a pathogenetic factor in the progress of ADOA.3

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OPA1 R445H mutation in optic atrophy associated with sensorineural deafness

Cited by 151 publications

References 20 publications

Neural and receptor cochlear potentials obtained by transtympanic electrocochleography in auditory neuropathy

Neural and receptor cochlear potentials obtained by transtympanic electrocochleography in auditory neuropathy

The many shapes of mitochondrial death

Mitochondrial Ca2+ uptake correlates with the severity of the symptoms in autosomal dominant optic atrophy

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