title: No Evidence for Association of SCO2 Heterozygosity with High-Grade Myopia or Other Diseases with Possible Mitochondrial Dysfunction.
abstract: SCO2 mutations cause recessively inherited cytochrome c oxidase deficiency. Recently Tran-Viet et al. proposed that heterozygosity for pathogenic SCO2 variants, including the common E140K variant, causes high-grade myopia. To investigate the association of SCO2 mutations with myopia, ophthalmic examinations were performed on 35 E140K carriers, one homozygous infant, and on a mouse model of Sco2 deficiency. Additionally, a screen for other putative effects of SCO2 heterozygosity was carried out by comparing the prevalence of the common E140K variant in a population of patients with undiagnosed diseases compatible with SCO2-related pathogenesis to that in a general population sample. High-grade myopia was not identified in any of the studied individuals. Of the carriers, 17 were emmetropic, and 18 possessed refractive errors. Additionally, no significant axial elongation indicative of high-grade myopia was found in mice carrying E129K (corresponding to E140K in humans) knock-in mutations. The prevalence of E140K carriers in the symptomatic cohort was evaluated as 1:103 (CI: 0.44-2.09) and did not differ significantly from the population prevalence (1:147, CI: 0.45-1.04).Our study demonstrates that heterozygosity for pathogenic SCO2 variants is not associated with high-grade myopia in either human patients or in mice.
authors.affiliation: Department of Medical Genetics, The Children's Memorial Health Institute, 04-730, Warsaw, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Piekutowska-Abramczuk
authors.affiliation: Department of Ophthalmology, The Children's Memorial Health Institute, 04-730, Warsaw, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Kocyła-Karczmarewicz
authors.affiliation: Department of Medical Genetics, The Children's Memorial Health Institute, 04-730, Warsaw, Poland.
authors.forename: Maja
authors.initials: M
authors.lastname: Małkowska
authors.affiliation: Department of Medical Genetics, The Children's Memorial Health Institute, 04-730, Warsaw, Poland.
authors.forename: Sylwia
authors.initials: S
authors.lastname: Łuczak
authors.affiliation: Department of Medical Genetics, The Children's Memorial Health Institute, 04-730, Warsaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Iwanicka-Pronicka
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, NY, 10032, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Siegmund
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, NY, 10032, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Ophthalmology, Columbia University Medical Center, New York, NY, 10032, USA.
authors.forename: Quan
authors.initials: Q
authors.lastname: Wen
authors.affiliation: Department of Ophthalmology, Columbia University Medical Center, New York, NY, 10032, USA.
authors.forename: Quan V
authors.initials: QV
authors.lastname: Hoang
authors.affiliation: Department of Ophthalmology, Columbia University Medical Center, New York, NY, 10032, USA.
authors.forename: Ronald H
authors.initials: RH
authors.lastname: Silverman
authors.affiliation: Department of Medical Genetics, The Children's Memorial Health Institute, 04-730, Warsaw, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Kowalski
authors.affiliation: Department of Medical Genetics, The Children's Memorial Health Institute, 04-730, Warsaw, Poland.
authors.forename: Olga
authors.initials: O
authors.lastname: Szczypińska
authors.affiliation: Department of Medical Genetics, The Children's Memorial Health Institute, 04-730, Warsaw, Poland.
authors.forename: Kamila
authors.initials: K
authors.lastname: Czornak
authors.affiliation: Department of Genetics, Institute of Psychiatry and Neurology, 02-957, Warsaw, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Zimowski
authors.affiliation: Department of Medical Genetics, Medical University of Warsaw, 02-106, Warsaw, Poland.
authors.forename: Rafał
authors.initials: R
authors.lastname: Płoski
authors.affiliation: Department of Child Neurology, Medical University of Silesia, 0-055, Katowice, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Pilch
authors.affiliation: Department of Medical Genetics, The Children's Memorial Health Institute, 04-730, Warsaw, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Ciara
authors.affiliation: Department of Genetics, Institute of Psychiatry and Neurology, 02-957, Warsaw, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Zaremba
authors.affiliation: Department of Medical Genetics, The Children's Memorial Health Institute, 04-730, Warsaw, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Krajewska-Walasek
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, NY, 10032, USA.|Department of Genetics and Development, Columbia University Medical Center, New York, NY, 10032, USA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Schon
authors.affiliation: Department of Medical Genetics, The Children's Memorial Health Institute, 04-730, Warsaw, Poland. e.pronicka@czd.pl.|Department of Pediatrics, Nutrition and Metabolic Diseases, The Children's Memorial Health Institute, 04-730, Warsaw, Poland. e.pronicka@czd.pl.
authors.forename: Ewa
authors.initials: E
authors.lastname: Pronicka
keywords: E140K carrier; Myopia; SCO2 gene variant; SMA negative