title: Stargardt disease-associated mutation spectrum of a Russian Federation cohort.
abstract: ABCA4-associated mutation screening is extensively performed in European, African, American and several other populations for various retinopathies. However, it has not been well studied in a Russian cohort. Using next-generation (325 genes inherited disease panel) and Sanger sequencing technologies for the first time we documented the spectrum of genetic variations in a Russian retinopathy cohort of 51 patients from 10 ethnic groups. We found ABCA4 variations in 70.5% cases and one case with BEST1 variation. Multiple ABCA4 variations, ABCA4 + RDH12, and ABCA4 + BEST1 variations are also observed and the disease severity is found proportionate to the variation burden. Ten novel ABCA4 variations are detected of which 8 belongs to non-Slavonian population. Most of the detected known variations are found in European and American Stargardt disease populations. No retinopathy causing variation is detected in 14 (27%) cases suggesting that in this Russian retinopathies cohort the causal variants could be in genes that are not covered by our 325 gene panel. Therefore, whole genome/exome analysis is required to identify novel retinopathy associated genes and provide better disease management for this heterogeneous cohort.
authors.affiliation: Moscow Helmholtz Research Institute of Eye Diseases, Sadovaya Chernogryazskaya Str. 14/19, Moscow 105062, Russia.
authors.forename: Inna V
authors.initials: IV
authors.lastname: Zolnikova
authors.affiliation: Research Centre for Medical Genetics, Moskvorechie Str. 1, Moscow 15478, Russia.
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Strelnikov
authors.affiliation: Posterior Eye Segment Diagnostics and Surgery Centre, 2nd Vladimirskaya Str. b.2, 4th Floor, Moscow 111123, Russia.
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Skvortsova
authors.affiliation: Research Centre for Medical Genetics, Moskvorechie Str. 1, Moscow 15478, Russia.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Tanas
authors.affiliation: Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology (IIOAB), Nonakuri, Purba Medinipur, WB 721172, India; Xcode Life Sciences, 3D Eldorado, 112 Nungambakkam High Road, Nungambakkam, Chennai, Tamil Nadu 600034, India. Electronic address: dr.barh@gmail.com.
authors.forename: Debmalya
authors.initials: D
authors.lastname: Barh
authors.affiliation: Moscow Helmholtz Research Institute of Eye Diseases, Sadovaya Chernogryazskaya Str. 14/19, Moscow 105062, Russia.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Rogatina
authors.affiliation: Moscow Helmholtz Research Institute of Eye Diseases, Sadovaya Chernogryazskaya Str. 14/19, Moscow 105062, Russia.
authors.forename: Irina V
authors.initials: IV
authors.lastname: Egorova
authors.affiliation: Moscow Helmholtz Research Institute of Eye Diseases, Sadovaya Chernogryazskaya Str. 14/19, Moscow 105062, Russia.
authors.forename: Darja V
authors.initials: DV
authors.lastname: Levina
authors.affiliation: Moscow Helmholtz Research Institute of Eye Diseases, Sadovaya Chernogryazskaya Str. 14/19, Moscow 105062, Russia.
authors.forename: Olga N
authors.initials: ON
authors.lastname: Demenkova
authors.affiliation: Bioinformatics Institute, Kantemirovskaya Str. b.2a, Saint Petersburg 197342, Russia.
authors.forename: Egor G
authors.initials: EG
authors.lastname: Prikaziuk
authors.affiliation: Оftalmic LLC, Bardina Str. 4, Moscow 119334, Russia.
authors.forename: Marianna E
authors.initials: ME
authors.lastname: Ivanova
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D004252:DNA Mutational Analysis; D059472:Exome / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008268:Macular Degeneration / Q000151:congenital* / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D012426:Russia / Q000453:epidemiology; D000080362:Stargardt Disease; D044465:White People
chemical_list: C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters
keywords: Gene mutation; Genotype-phenotype correlation; Next-generation sequencing; Retinal dystrophies; Retinopathy; Stargardt disease