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      Genetic and clinical characterization of mainland Chinese patients with sialidosis type 1

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          Abstract

          Background

          Sialidosis type 1 is a rare inherited disorder with a high disability. No genetically confirmed mainland Chinese patient with sialidosis type 1 has been reported. This study evaluated the phenotypes and genotypes of mainland Chinese patients with sialidosis type 1.

          Methods

          It was a retrospective case series study. Four unrelated patients were enrolled. Comprehensive clinical evaluations and molecular genetic analysis of the NEU1 gene were performed.

          Results

          Three out of four patients presented progressive myoclonus epilepsy. The best‐corrected visual acuity ranged from 20/2000 to 20/25. Punctate cataracts were found in all of the patients. Distinct macular cherry red spots were observed in three patients by fundoscopy, and a relatively normal fundus was revealed in one patient. Optical coherence tomography (OCT) showed increased reflectivity of the nerve fiber and ganglion cell layers, and fundus autofluorescence (FAF) revealed hyperautofluorescent areas surrounding the fovea in all of the patients. Only superficial retinal vessels can be observed using OCT angiography; the deeper capillary plexus could not be observed. Visual evoked potential revealed varying degrees of decreased amplitude and/or prolonged latency of P100 or P2 waves. The most frequent sequence variant identified was c.544A>G (p.S182G) (NM_000434.3).

          Conclusions

          Our study first described the ophthalmic and neurologic characteristics of a small cohort of unrelated mainland Chinese patients with sialidosis type 1. We found that c.544A>G (p. S182G) might be a hotspot variant in Chinese patients. The accumulation of metabolic products in the nerve fiber and ganglion cell layers is a characteristic ocular finding that could be sensitively detected by OCT and FAF imaging.

          Abstract

          Sialidosis is a rare inherited disorder and no genetically confirmed mainland Chinese patient with sialidosis type 1 has been reported. Our study first described the ophthalmic and neurologic characteristics and mutation spectrum of a small cohort of unrelated mainland Chinese patients with sialidosis type 1 and found that the accumulation of metabolic products in the lens, ganglion cell and retinal nerve fiber layer are characteristic ocular findings, and the latter could be sensitively detected by optical coherence tomography and fundus autofluorescence.

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          Most cited references31

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          Development of a gene-editing approach to restore vision loss in Leber congenital amaurosis type 10

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            Progressive myoclonic epilepsies: a review of genetic and therapeutic aspects.

            The progressive myoclonic epilepsies (PMEs) are a group of symptomatic generalised epilepsies caused by rare disorders, most of which have a genetic component, a debilitating course, and a poor outcome. Challenges with PME arise from difficulty with diagnosis, especially in the early stages of the illness, and further problems of management and drug treatment. Recent advances in molecular genetics have helped achieve better understanding of the different disorders that cause PME. We review the PMEs with emphasis on updated genetics, diagnosis, and therapeutic options.
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              Lysosomal multienzyme complex: pros and cons of working together.

              The ubiquitous distribution of lysosomes and their heterogeneous protein composition reflects the versatility of these organelles in maintaining cell homeostasis and their importance in tissue differentiation and remodeling. In lysosomes, the degradation of complex, macromolecular substrates requires the synergistic action of multiple hydrolases that usually work in a stepwise fashion. This catalytic machinery explains the existence of lysosomal enzyme complexes that can be dynamically assembled and disassembled to efficiently and quickly adapt to the pool of substrates to be processed or degraded, adding extra tiers to the regulation of the individual protein components. An example of such a complex is the one composed of three hydrolases that are ubiquitously but differentially expressed: the serine carboxypeptidase, protective protein/cathepsin A (PPCA), the sialidase, neuraminidase-1 (NEU1), and the glycosidase β-galactosidase (β-GAL). Next to this 'core' complex, the existence of sub-complexes, which may contain additional components, and function at the cell surface or extracellularly, suggests as yet unexplored functions of these enzymes. Here we review how studies of basic biological processes in the mouse models of three lysosomal storage disorders, galactosialidosis, sialidosis, and GM1-gangliosidosis, revealed new and unexpected roles for the three respective affected enzymes, Ppca, Neu1, and β-Gal, that go beyond their canonical degradative activities. These findings have broadened our perspective on their functions and may pave the way for the development of new therapies for these lysosomal storage disorders.
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                Author and article information

                Contributors
                hrfsui@163.com
                Journal
                Mol Genet Genomic Med
                Mol Genet Genomic Med
                10.1002/(ISSN)2324-9269
                MGG3
                Molecular Genetics & Genomic Medicine
                John Wiley and Sons Inc. (Hoboken )
                2324-9269
                26 May 2020
                August 2020
                : 8
                : 8 ( doiID: 10.1002/mgg3.v8.8 )
                : e1316
                Affiliations
                [ 1 ] Department of Ophthalmology Peking Union Medical College Hospital Chinese Academy of Medical Sciences Beijing China
                [ 2 ] Key Laboratory of Ocular Fundus Diseases Chinese Academy of Medical Sciences & Peking Union Medical College Beijing China
                [ 3 ] Department of Ophthalmology Eye and ENT Hospital of Fudan University Shanghai China
                [ 4 ] Department of Neurology Peking Union Medical College Hospital Chinese Academy of Medical Sciences Beijing China
                Author notes
                [*] [* ] Correspondence

                Ruifang Sui, 1 Shuai Fu Yuan, Department of Ophthalmology, Peking Union Medical College Hospital, Beijing 100730, China.

                Email: hrfsui@ 123456163.com

                Author information
                https://orcid.org/0000-0002-6659-0926
                Article
                MGG31316
                10.1002/mgg3.1316
                7434748
                32453490
                2971c1c0-e2a8-46a3-ae06-9a631b5ad13f
                © 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 10 February 2020
                : 25 April 2020
                : 28 April 2020
                Page count
                Figures: 2, Tables: 2, Pages: 10, Words: 6251
                Funding
                Funded by: CAMS Innovation Fund for Medical Sciences
                Award ID: 2016‐12M‐1‐002
                Funded by: Non‐profit Central Research Institute Fund of Chinese Academy of Medical Sciences
                Award ID: 2018PT32029
                Funded by: National Natural Science Foundation of China , open-funder-registry 10.13039/501100001809;
                Award ID: 81873687
                Funded by: Natural Science Foundation of Beijing Municipality , open-funder-registry 10.13039/501100004826;
                Award ID: 7202159
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                August 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.6 mode:remove_FC converted:18.08.2020

                faf,macular cherry red spot,oct,octa,sialidosis type 1
                faf, macular cherry red spot, oct, octa, sialidosis type 1

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