Case of phenotype of optic nerve atrophy due to mutation in С19orf12 gene (neurodegeneration with the brain iron accumulation (nbia))
M.E. Ivanova1, V.V. Kadyshev2, D.S. Atarshchikov3, I.V. Zolnikova4, N.P. Akchurina4, N.K. Serova5, F.A. Konovalov6, E.R. Lozier6, E.A. Pomerantseva7, N.V. Vetrova7, D. Barh8, L.M. Balashova9, J.M. Salmasi10
1 LLC “Oftalmic”, Moscow, Russian Federation
2 Research Centre for Medical Genetics, Moscow, Russian Federation
3 Central Clinical Hospital under Presidential Affairs, Moscow, Russian Federation
4 Moscow Helmholtz Research Institute of Eye Diseases, Moscow, Russian Federation
5 N.N. Burdenko National Medical Research Center of Neurosurgery, Moscow, Russian
Federation
6 Independent Clinical Bioinformatics Laboratory, Moscow, Russian Federation
7 Center for Genetics and Reproductive Medicine “Genetiko”, Moscow, Russian
Federation
8 Institute of Integrative Omics and Applied Biotechnology (IIOAB), Bangalore, India
9 Non-profit partnership International Scientific and Practical Center for the Proliferation
of Tissues of Russia, Moscow, Russian Federation
10Pirogov Russian National Research Medical University, Moscow, Russian Federation
The article describes the clinical case of optic atrophy due to a homozygous mutation in exon 3 of the C19orf12 gene (chr19: 30193863AACAGCCCCCCG> A, rs515726204), the frequency of which in the ExAC control sample is 0.0074. With this mutation, a frameshift occurs at 69-th position (p.Gly69fs, NM_001031726.3), which usually leads to neurodegeneration with the brain iron accumulation (NBIA), type 4 (OMIM: 614298). In described clinical case the main complaint of patient was visual impairment, with magnetic resonance imaging patient revealed only the expansion of the sellar fossa. The vision of 7-year-old boy decreased significantly for 2 years without any apparent reasons, spectacle correction did not give an improvement in vision to 100%. During the examination partial atrophy of the optic nerves was revealed, consultations were conducted with a neurologist, neurophthalmologist. Hyperreflexia, gait changes, and a slight delay in speech development were also revealed. No other clinical neurological symptoms were observed. The article describes a detailed ophthalmic clinical picture, discusses diagnostic and therapeutic tactics.
Keywords: optic nerve atrophy, neurodegeneration with the brain iron accumulation, NBIA, mutation, gene, C19orf12.
For citation: Ivanova M.E., Kadyshev V.V., Atarshchikov D.S. et al. Case of phenotype of optic nerve atrophy due to mutation in С19orf12 gene (neurodegeneration with the brain iron accumulation (nbia)). Russian Journal of Clinical Ophthalmology. 2020;20(1):–36. DOI: 10.32364/2311-7729-2020-20-1-33-36.
About the authors:
1Marianna E. Ivanova — MD, PhD, Head of CRO, ORCID iD 0000-0002-1089-4293;
2Vitaly V. Kadyshev — MD, PhD, Senior Researcher ophthalmologist, geneticist, ORCID iD 0000-0001-7765-3307;
3Dmitry S. Atarshchikov — MD, PhD, ophthalmologist, ORCID iD 0000-0003-4401-9099;
4Inna V. Zolnikova — MD, PhD, ophthalmologist, Senior Researcher, ORCID iD 0000-0001-7264-396X;
4Natalya P. Akchurina — MD, PhD, ophthalmologist, ORCID iD 0000-0002-6726-4612;
5Natalya K. Serova — MD, PhD, neuroophthalmologist, Chief Researcher, ORCID iD 0000-0003-0148-7298;
6Fedor A. Konovalov — PhD, Head of bioinformatics department, ORCID iD 0000-0001-6414-436X;
6Ekaterina R. Lozier — bioinformatician, ORCID iD 0000-0003-2901-0539;
7Ekaterina A. Pomerantseva — MD, PhD, geneticist, ORCID iD 0000-0002-6765-7133;
7Natalya V. Vetrova — MD, PhD, geneticist, ORCID iD 0000-0002-7012-2359;
8Debmalya Barh — PhD, Head of OMICs analysis department, ORCID iD 0000-0002-2557-7768;
9Larisa M. Balashova — MD, PhD, Professor, Head of the Center, ORCID iD 0000-0001-9349-7092;
10Jean M. Salmasi — MD, PhD, Professor, Head of Patho-physiology Department, ORCID iD 0000-0001-8524-0019.
1LLC “Oftalmic”. 47/3–3, Leningradsky Prospekt, Moscow, 125167, Russian Federation.
2Research Centre for Medical Genetics. 1, Moskvorechie str., Moscow, 115478, Russian Federation.
3Central Clinical Hospital for Presidential Affairs. 15, Marshala Timoshenko str., Moscow,121359, Russian Federation.
4Moscow Helmholtz Research Institute of Eye Diseases. 14/19, Sadovaya-Chernogryazskaya str., Moscow, 105062, Russian Federation.
5N.N. Burdenko National Medical Research Center of Neurosurgery. 16, 4-th Tverskaya-Yamskaya str., Moscow, 125047, Russian Federation.
6Independent Clinical Bioinformatics Laboratory, 21/1, Marshala Katukova str., Moscow, 123181, Russian Federation.
7Center for Genetics and Reproductive Medicine “Genetiko”. 3/1, Gubkina str., Moscow, 119333, Russian Federation.
8Institute of Integrative Omics and Applied Biotechnology (IIOAB). 209, Cholanayakanahalli str., Bangalore, 560032, India.
9Non-profit partnership International Scientific and Practical Center for the Proliferation of Tissues of Russia. 29/14, Prechistenka str., Moscow, 119034, Russian Federation.
10Pirogov Russian National Research Medical University. 1, Ostrovityanov str., Moscow, 117513, Russian Federation.
Contact information: Marianna E. Ivanova, e-mail: info@ oftalmic.ru. Financial Disclosure: Marianna E. Ivanova is the collaborator of LLC “Oftalmic”. Fedor A. Konovalov, Ekaterina R. Lozier are employees of the Independent Clinical Bioinformatics Laboratory, Ekaterina A. Pomerantseva, Natalya V. Vetrova are employees of the “Genetiko” Center. Other authors declare that there is no conflict of interests. Received 14.09.2019.
2. Deschauer M., Gaul C., Behrmann C. et al. C19orf12 mutations in neurodegeneration with brain iron accumulation mimicking juvenile amyotrophic lateral sclerosis. J Neurol. 2012;259:2434–2439. DOI: 10.1007/s00415-012-6521-7.
3. Hartig M.B., Iuso A., Haack T. et al. Absence of an orphan mitochondrial protein, c19orf12, causes a distinct clinical subtype of neurodegeneration with brain iron accumulation. Am J Hum Genet. 2011;89:543–550. DOI: 10.1016/j.ajhg.2011.09.007.
4. Hogarth P., Gregory A., Kruer M.C. et al. New NBIA subtype: genetic, clinical, pathologic, and radiographic features of MPAN. Neurology. 2013;80:268–275. DOI: 10.1212/WNL.0b013e31827e07be.
5. Landouré G., Zhu P.P., Lourenço C.M. et al. Hereditary spastic paraplegia type 43 (SPG43) is caused by mutation in C19orf12. Hum Mutat. 2013;34:1357–1360. DOI: 10.1002/humu.22378.
6. Skowronska M., Kmiec T., Jurkiewicz E. et al. Evolution and novel radiological changes of neurodegeneration associated with mutations in C19orf12. Parkinsonism Relat Disord. 2017;39:71–76. DOI: 10.1016/j.parkreldis.2017.03.013.
7. Langwinska-Wosko E., Skowronska M., Kmiec T., Czlonkowska A. Retinal and optic nerve abnormalities in neurodegeneration associated with mutations in C19orf12 (MPAN). J Neurol Sci. 2016;370:237–240. DOI: 10.1016/j.jns.2016.09.046.
8. Schneider S.A., Dusek P., Hardy J. et al. Genetics and Pathophysiology of Neurodegeneration with Brain Iron Accumulation (NBIA). Curr Neuropharmacol. 2013;11(1):59–79. DOI: 10.2174/157015913804999469.
9. Protein Homology/analogy Recognition Engine V 2.0. (Electronic resource). URL: http://www.sbg.bio.ic.ac.uk/phyre2. Access date: 15.12.2019.
10. Dusek P., Mekle R., Kmiec T. et al. Brain iron and metabolic abnormalities in C19orf12 mutation carriers: A 7.0 tesla MRI study in mitochondrial membrane protein-associated neurodegeneration. Mov Disord. 2019 [epub ahead of print]. DOI: 10.1002/mds.27827.
This work is licensed under a Creative Commons «Attribution» 4.0 License.