Autosomal dominant optic atrophy plus due to the novel OPA1 variant c.1463G>C
Tóm tắt
OPA1 variants most frequently manifest phenotypically with pure autosomal dominant optic atrophy (ADOA) or with ADOA plus. The most frequent abnormalities in ADOA plus in addition to the optic nerve affection include hypoacusis, migraine, myopathy, and neuropathy. Hypertelorism and atrophy of the acoustic nerve have not been reported. The patient is a 48yo Caucasian female with slowly progressive, visual impairment since childhood, bilateral hypoacusis since age 10y, and classical migraine since age 20y. The family history was positive for diabetes (father, mother) and visual impairment (daughter). Clinical examination revealed hypertelorism, visual impairment, hypoacusis, tinnitus, weakness for elbow flexion and finger straddling, and generally reduced tendon reflexes. MRI of the cerebrum was non-informative but hypoplasia of the acoustic nerve bilaterally was described. Visually-evoked potentials revealed markedly prolonged P100-latencies bilaterally. Acoustically-evoked potentials were distorted with poor reproducibility and prolonged latencies. Muscle biopsy revealed reduced activities of complexes I, II, and IV. Genetic work-up revealed the novel variant c.1463G>C in the OPA1 gene. This case provides novel information regarding the genotype of ADOA plus. The novel OPA1 variant c.1463G>C not only manifests with visual impairment, hypoacusis, migraine, and myopathy, but also with hypertelorisms and acoustic nerve atrophy.
Tài liệu tham khảo
Ahmad KE, Davis RL, Sue CM (2015) A novel OPA1 mutation causing variable age of onset autosomal dominant optic atrophy plus in an Australian family. J Neurol 262:2323–2328
Amati-Bonneau P, Valentino ML, Reynier P, Gallardo ME, Bornstein B, Boissière A, Campos Y, Rivera H, de la Aleja JG, Carroccia R, Iommarini L, Labauge P, Figarella-Branger D, Marcorelles P, Furby A, Beauvais K, Letournel F, Liguori R, La Morgia C, Montagna P, Liguori M, Zanna C, Rugolo M, Cossarizza A, Wissinger B, Verny C, Schwarzenbacher R, Martín MA, Arenas J, Ayuso C, Garesse R, Lenaers G, Bonneau D, Carelli V (2008) OPA1 mutations induce mitochondrial DNA instability and optic atrophy 'plus' phenotypes. Brain 131:338–351
Carelli V, Musumeci O, Caporali L, Zanna C, La Morgia C, Del Dotto V, Porcelli AM, Rugolo M, Valentino ML, Iommarini L, Maresca A, Barboni P, Carbonelli M, Trombetta C, Valente EM, Patergnani S, Giorgi C, Pinton P, Rizzo G, Tonon C, Lodi R, Avoni P, Liguori R, Baruzzi A, Toscano A, Zeviani M (2015) Syndromic parkinsonism and dementia associated with OPA1 missense mutations. Ann Neurol 78:21–38
Delettre C, Lenaers G, Griffoin JM, Gigarel N, Lorenzo C, Belenguer P, Pelloquin L, Grosgeorge J, Turc-Carel C, Perret E, Astarie-Dequeker C, Lasquellec L, Arnaud B, Ducommun B, Kaplan J, Hamel CP (2000) Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy. Nat Genet 26:207–210
Duvezin-Caubet S, Jagasia R, Wagener J, Hofmann S, Trifunovic A, Hansson A, Chomyn A, Bauer MF, Attardi G, Larsson NG, Neupert W, Reichert AS (2006) Proteolytic processing of OPA1 links mitochondrial dysfunction to alterations in mitochondrial morphology. J Biol Chem 281:37972–37979
Finsterer J, Mancuso M, Pareyson D, Burgunder JM, Klopstock T (2018) Mitochondrial disorders of the retinal ganglion cells and the optic nerve. Mitochondrion 42:1–10
Gerber S, Charif M, Chevrollier A, Chaumette T, Angebault C, Kane MS, Paris A, Alban J, Quiles M, Delettre C, Bonneau D, Procaccio V, Amati-Bonneau P, Reynier P, Leruez S, Calmon R, Boddaert N, Funalot B, Rio M, Bouccara D, Meunier I, Sesaki H, Kaplan J, Hamel CP, Rozet JM, Lenaers G (2017) Mutations in DNM1L, as in OPA1, result in dominant optic atrophy despite opposite effects on mitochondrial fusion and fission. Brain 140:2586–2596
Ham M, Han J, Osann K, Smith M, Kimonis V (2019) Meta-analysis of genotype-phenotype analysis of OPA1 mutations in autosomal dominant optic atrophy. Mitochondrion 46:262–269
Hudson G, Amati-Bonneau P, Blakely EL, Stewart JD, He L, Schaefer AM, Griffiths PG, Ahlqvist K, Suomalainen A, Reynier P, McFarland R, Turnbull DM, Chinnery PF, Taylor RW (2008) Mutation of OPA1 causes dominant optic atrophy with external ophthalmoplegia, ataxia, deafness and multiple mitochondrial DNA deletions: a novel disorder of mtDNA maintenance. Brain 131:329–337
Li H, Jones EM, Li H, Yang L, Sun Z, Yuan Z, Chen R, Dong F, Sui R (2018) Clinical and genetic features of eight Chinese autosomal-dominant optic atrophy pedigrees with six novel OPA1 pathogenic variants. Ophthalmic Genet 39:569–576
Liskova P, Ulmanova O, Tesina P, Melsova H, Diblik P, Hansikova H, Tesarova M, Votruba M (2013) Novel OPA1 missense mutation in a family with optic atrophy and severe widespread neurological disorder. Acta Ophthalmol 91:e225–e231
Nasca A, Rizza T, Doimo M, Legati A, Ciolfi A, Diodato D, Calderan C, Carrara G, Lamantea E, Aiello C, Di Nottia M, Niceta M, Lamperti C, Ardissone A, Bianchi-Marzoli S, Iarossi G, Bertini E, Moroni I, Tartaglia M, Salviati L, Carrozzo R, Ghezzi D (2017) Not only dominant, not only optic atrophy: expanding the clinical spectrum associated with OPA1 mutations. Orphanet J Rare Dis 12(1):89. https://doi.org/10.1186/s13023-017-0641-1.
Pretegiani E, Rosini F, Rufa A, Gallus GN, Cardaioli E, Da Pozzo P, Bianchi S, Serchi V, Collura M, Franceschini R, Bianchi Marzoli S, Dotti MT, Federico A (2017) Genotype-phenotype and OCT correlations in autosomal dominant optic atrophy related to OPA1 gene mutations: report of 13 Italian families. J Neurol Sci 382:29–35
Santarelli R, Rossi R, Scimemi P, Cama E, Valentino ML, La Morgia C, Caporali L, Liguori R, Magnavita V, Monteleone A, Biscaro A, Arslan E, Carelli V (2015) OPA1-related auditory neuropathy: site of lesion and outcome of cochlear implantation. Brain 138:563–576
Spiegel R, Saada A, Flannery PJ, Burté F, Soiferman D, Khayat M, Eisner V, Vladovski E, Taylor RW, Bindoff LA, Shaag A, Mandel H, Schuler-Furman O, Shalev SA, Elpeleg O, Yu-Wai-Man P (2016) Fatal infantile mitochondrial encephalomyopathy, hypertrophic cardiomyopathy and optic atrophy associated with a homozygous OPA1 mutation. J Med Genet 53:127–131
Yu-Wai-Man P, Griffiths PG, Gorman GS, Lourenco CM, Wright AF, Auer-Grumbach M, Toscano A, Musumeci O, Valentino ML, Caporali L, Lamperti C, Tallaksen CM, Duffey P, Miller J, Whittaker RG, Baker MR, Jackson MJ, Clarke MP, Dhillon B, Czermin B, Stewart JD, Hudson G, Reynier P, Bonneau D, Marques WJ, Lenaers G, McFarland R, Taylor RW, Turnbull DM, Votruba M, Zeviani M, Carelli V, Bindoff LA, Horvath R, Amati-Bonneau P, Chinnery PF (2010) Multi-system neurological disease is common in patients with OPA1 mutations. Brain 133:771–786