Recessive optic atrophy, sensorimotor neuropathy and cataract associated with novel compound heterozygous mutations in OPA1

Lee,Jinho; Jung,Sung‑Chul; Hong,Young  Bin; Yoo,Jeong  Hyun; Koo,Heasoo; Lee,Ja  Hyun; Hong,Hyun  Dae; Kim,Sang‑Beom; Chung,Ki  Wha; Choi,Byung‑Ok

doi:10.3892/mmr.2016.5209

July-2016 Volume 14 Issue 1

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July-2016 Volume 14 Issue 1

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Article Open Access

Recessive optic atrophy, sensorimotor neuropathy and cataract associated with novel compound heterozygous mutations in OPA1

Authors:
- Jinho Lee
- Sung‑Chul Jung
- Young Bin Hong
- Jeong Hyun Yoo
- Heasoo Koo
- Ja Hyun Lee
- Hyun Dae Hong
- Sang‑Beom Kim
- Ki Wha Chung
- Byung‑Ok Choi
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Affiliations: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135‑710, Republic of Korea, Department of Biochemistry, Ewha Womans University School of Medicine, Seoul 120‑750, Republic of Korea, Department of Radiology, Ewha Womans University School of Medicine, Seoul 120‑750, Republic of Korea, Department of Pathology, Ewha Womans University School of Medicine, Seoul 120‑750, Republic of Korea, Department of Biological Science, Kongju National University, Konju, Chungnam 314‑701, Republic of Korea, Department of Neurology, Kyung Hee University College of Medicine, Seoul 143‑601, Republic of Korea

Copyright: © Lee et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Pages: 33-40
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Published online on: May 4, 2016

https://doi.org/10.3892/mmr.2016.5209
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Abstract

Mutations in the optic atrophy 1 gene (OPA1) are associated with autosomal dominant optic atrophy and 20% of patients demonstrate extra-ocular manifestations. In addition to these autosomal dominant cases, only a few syndromic cases have been reported thus far with compound heterozygous OPA1 mutations, suggestive of either recessive or semi‑dominant patterns of inheritance. The majority of these patients were diagnosed with Behr syndrome, characterized by optic atrophy, ataxia and peripheral neuropathy. The present study describes a 10-year-old boy with Behr syndrome presenting with early‑onset severe optic atrophy, sensorimotor neuropathy, ataxia and congenital cataracts. He had optic atrophy and was declared legally blind at six years old. Electrophysiological, radiological, and histopathological findings were compatible with axonal sensorimotor polyneuropathy. At birth, he presented with a congenital cataract, which has not been previously described in patients with OPA1 mutations. Whole exome sequencing indicated a pair of novel compound heterozygous mutations: p.L620fs*13 (c.1857‑1858delinsT) and p.R905Q (c.G2714A). Neither mutation was observed in controls (n=300), and thus, they were predicted to be pathogenic by multiple in silico analyses. The mutation sites were highly conserved throughout different vertebrate species. The patients parents did not have any ophthalmic or neurologic symptoms and the results of electrophysiological studies were normal, suggestive of an autosomal recessive pattern of inheritance. The present study identified novel compound heterozygous OPA1 mutations in a patient with recessive optic atrophy, sensorimotor neuropathy and congenital cataracts, indicating an expansion of the clinical spectrum of pathologies associated with OPA1 mutations. Thus, OPA1 gene screening is advisable in the workup of patients with recessive optic atrophy, particularly with Behr syndrome and cataracts.

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1	Lenaers G, Hamel C, Delettre C, Amati-Bonneau P, Procaccio V, Bonneau D, Reynier P and Milea D: Dominant optic atrophy. Orphanet J Rare Dis. 7:462012. View Article : Google Scholar : PubMed/NCBI
2	Eiberg H, Kjer B, Kjer P and Rosenberg T: Dominant optic atrophy (OPA1) mapped to chromosome 3q region. I. Linkage analysis. Hum Mol Genet. 3:977–980. 1994. View Article : Google Scholar : PubMed/NCBI
3	Yu-Wai-Man P, Griffiths PG, Gorman GS, Lourenco CM, Wright AF, Auer-Grumbach M, Toscano A, Musumeci O, Valentino ML, Caporali L, et al: Multi-system neurological disease is common in patients with OPA1 mutations. Brain. 133:771–786. 2010. View Article : Google Scholar : PubMed/NCBI
4	Pesch UE, Leo-Kottler B, Mayer S, Jurklies B, Kellner U, Apfelstedt-Sylla E, Zrenner E, Alexander C and Wissinger B: OPA1 mutations in patients with autosomal dominant optic atrophy and evidence for semi-dominant inheritance. Hum Mol Genet. 10:1359–1368. 2001. View Article : Google Scholar : PubMed/NCBI
5	Schaaf CP, Blazo M, Lewis RA, Tonini RE, Takei H, Wang J, Wong LJ and Scaglia F: Early-onset severe neuromuscular phenotype associated with compound heterozygosity for OPA1 mutations. Mol Genet Metab. 103:383–387. 2011. View Article : Google Scholar : PubMed/NCBI
6	Bonneau D, Colin E, Oca F, Ferré M, Chevrollier A, Guéguen N, Desquiret-Dumas V, N'Guyen S, Barth M, Zanlonghi X, et al: Early-onset Behr syndrome due to compound heterozygous mutations in OPA1. Brain. 137:e3012014. View Article : Google Scholar : PubMed/NCBI
7	Beh r C: Die komplizierte, hereditäre-familiäre Optikusatrophie des Kindesalters-ein bisher nicht beschriebener Symptomkomplex. Klin Mbl Augenheilkd. 39:138–60. 1909.In German.
8	Thomas PK, Workman JM and Thage O: Behr's syndrome. A family exhibiting pseudodominant inheritance. J Neurol Sci. 64:137–148. 1984. View Article : Google Scholar : PubMed/NCBI
9	Marelli C, Amati-Bonneau P, Reynier P, Layet V, Layet A, Stevanin G, Brissaud E, Bonneau D, Durr A and Brice A: Heterozygous OPA1 mutations in Behr syndrome. Brain. 134:e1692011.author reply e170. View Article : Google Scholar
10	Choi BO, Koo SK, Park MH, Rhee H, Yang SJ, Choi KG, Jung SC, Kim HS, Hyun YS, Nakhro K, et al: Exome sequencing is an efficient tool for genetic screening of Charcot-Marie-Tooth disease. Hum Mutat. 33:1610–1615. 2012. View Article : Google Scholar : PubMed/NCBI
11	Delettre C, Lenaers G, Griffoin JM, Gigarel N, Lorenzo C, Belenguer P, Pelloquin L, Grosgeorge J, Turc-Carel C, Perret E, et al: Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy. Nat Genet. 26:207–210. 2000. View Article : Google Scholar : PubMed/NCBI
12	Amati-Bonneau P, Milea D, Bonneau D, Chevrollier A, Ferré M, Guillet V, Gueguen N, Loiseau D, de Crescenzo MA, Verny C, et al: OPA1-associated disorders: Phenotypes and pathophysiology. Int J Biochem Cell Biol. 41:1855–1865. 2009. View Article : Google Scholar : PubMed/NCBI
13	Lloyd IC, Goss-Sampson M, Jeffrey BG, Kriss A, Russell-Eggitt I and Taylor D: Neonatal cataract: Aetiology, pathogenesis and management. Eye (Lond). 6:184–196. 1992. View Article : Google Scholar
14	Chan WH, Biswas S, Ashworth JL and Lloyd IC: Congenital and infantile cataract: Aetiology and management. Eur J Pediatr. 171:625–630. 2012. View Article : Google Scholar : PubMed/NCBI
15	Aijaz S, Erskine L, Jeffery G, Bhattacharya SS and Votruba M: Developmental expression profile of the optic atrophy gene product: OPA1 is not localized exclusively in the mammalian retinal ganglion cell layer. Invest Ophthalmol Vis Sci. 45:1667–1673. 2004. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Recessive optic atrophy, sensorimotor neuropathy and cataract associated with novel compound heterozygous mutations in OPA1

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