Detailed genetic characteristics of an international large cohort of patients with Stargardt disease: ProgStar study report 8. Issue 3 (20th June 2018)

• Record Type: Journal Article
• Authors: Fujinami, Kaoru; Strauss, Rupert W; Chiang, John (Pei-Wen); Audo, Isabelle S; Bernstein, Paul S; Birch, David G; Bomotti, Samantha M; Cideciyan, Artur V; Ervin, Ann-Margret; Marino, Meghan J; Sahel, José-Alain; Mohand-Said, Saddek; Sunness, Janet S; Traboulsi, Elias I; West, Sheila; Wojciechowski, Robert; Zrenner, Eberhart; Michaelides, Michel; Scholl, Hendrik P N
• Other Names: author non-byline.; Scholl Hendrik PN author non-byline.; Strauss Rupert W author non-byline.; Wolfson Yulia author non-byline.; Bittencourt Millena author non-byline.; Shah Syed Mahmood author non-byline.; Ahmed Mohamed author non-byline.; Schönbach Etienne author non-byline.; Fujinami Kaoru author non-byline.; Traboulsi Elias author non-byline.; Ehlers Justis author non-byline.; Marino Meghan author non-byline.; Crowe Susan author non-byline.; Briggs Rachael author non-byline.; Borer Angela author non-byline.; Pinter Anne author non-byline.; Fecko Tami author non-byline.; Burgnoni Nikki author non-byline.; Sunness Janet S author non-byline.; Applegate Carol author non-byline.; Russell Leslie author non-byline.; Michaelides Michel author non-byline.; Esposti Simona Degli author non-byline.; Moore Anthony author non-byline.; Webster Andrew author non-byline.; Connor Sophie author non-byline.; Barnfield Jade author non-byline.; Salchi Zaid author non-byline.; Alfageme Clara author non-byline.; McCudden Victoria author non-byline.; Pefkianaki Maria author non-byline.; Aboshiha Jonathan author non-byline.; Liew Gerald author non-byline.; Holder Graham author non-byline.; Robson Anthony author non-byline.; King Alexa author non-byline.; Cajas Narvaez Daniela Ivanova author non-byline.; Barnard Katy author non-byline.; Grigg Catherine author non-byline.; Dunbar Hannah author non-byline.; Obadeyi Yetunde author non-byline.; Girard-Claudon Karine author non-byline.; Swann Hilary author non-byline.; Rughani Avani author non-byline.; Amoah Charles author non-byline.; Carrington Dominic author non-byline.; Bibi Kanom author non-byline.; Co Emerson Ting author non-byline.; Illiyas Mohamed Nafaz author non-byline.; Begum Hamida author non-byline.; Carter Andrew author non-byline.; Georgiou Anne author non-byline.; Lewis Selma author non-byline.; Shaheen Saddaf author non-byline.; Shinmar Harpreet author non-byline.; Burton Linda author non-byline.; Bernstein Paul author non-byline.; Wegner Kimberley author non-byline.; 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Mohand-Said Saddek author non-byline.; Audo Isabelle author non-byline.; Laurent-Coriat Caroline author non-byline.; Sliesoraityte Ieva author non-byline.; Zeitz Christina author non-byline.; Boyard Fiona author non-byline.; Tran Minh Ha author non-byline.; Chapon Mathias author non-byline.; Chaumette Céline author non-byline.; Amaudruz Juliette author non-byline.; Ganem Victoria author non-byline.; Sancho Serge author non-byline.; Girmens Aurore author non-byline.; Wojciechowski Robert author non-byline.; Khan Shazia author non-byline.; Emmert David G author non-byline.; Cain Dennis author non-byline.; Herring Mark author non-byline.; Bassinger Jennifer author non-byline.; Liberto Lisa author non-byline.; West Sheila K author non-byline.; Ervin Ann-Margret author non-byline.; Munoz Beatriz author non-byline.; Kong Xiangrong author non-byline.; Dreger Kurt author non-byline.; Jones Jennifer author non-byline.; Burke Robert author non-byline.; Sadda Srinivas author non-byline.; Ip Michael S author non-byline.; Jha Anamika author non-byline.; Ho Alex author non-byline.; Kramer Brendan author non-byline.; Lam Ngoc author non-byline.; Tawdros Rita author non-byline.; Zhou Yong Dong author non-byline.; Carmona Johana author non-byline.; Uji Akihito author non-byline.; Hariri Amirhossein author non-byline.; Lock Amy author non-byline.; Elshafei Anthony author non-byline.; Ganegoda Anushika author non-byline.; Petrossian Christine author non-byline.; Jenkins Dennis author non-byline.; Strnad Edward author non-byline.; Baghdasaryan Elmira author non-byline.; Ito Eric author non-byline.; Samson Feliz author non-byline.; Blanquel Gloria author non-byline.; Akil Handan author non-byline.; Melendez Jhanisus author non-byline.; Lei Jianqin author non-byline.; Huang Jianyan author non-byline.; Chau Jonathan author non-byline.; Falavarjani Khalil G author non-byline.; Espino Kristina author non-byline.; Li Manfred author non-byline.; Mendoza Maria author non-byline.; Nittala Muneeswar Gupta author non-byline.; Roded Netali author non-byline.; Saleh Nizar author non-byline.; Huang Ping author non-byline.; Pitetta Sean author non-byline.; Balasubramanian Siva author non-byline.; Leahy Sophie author non-byline.; Srinivas Sowmya J author non-byline.; Velaga Swetha B author non-byline.; Margaryan Teresa author non-byline.; Tepelus Tudor author non-byline.; Brown Tyler author non-byline.; Fan Wenying author non-byline.; Murillo Yamileth author non-byline.; Shi Yue author non-byline.; Aguilar Katherine author non-byline.; Chan Cynthia author non-byline.; Santos Lisa author non-byline.; Seo Brian author non-byline.; Sison Christopher author non-byline.; Perez Silvia author non-byline.; Chao Stephanie author non-byline.; Miyasato Kelly author non-byline.; Higgins Julia author non-byline.; Luna Zoila author non-byline.; Menchaca Anita author non-byline.; Gonzalez Norma author non-byline.; Robledo Vicky author non-byline.; Carig Karen author non-byline.; Baker Kirstie author non-byline.; Ellenbogen David author non-byline.; Bluemel Daniel author non-byline.; Sanford Theo author non-byline.; Linares Daisy author non-byline.; Tran Mei author non-byline.; Nava Lorane author non-byline.; Oberoi Michelle author non-byline.; Romero Mark author non-byline.; Chiguil Vivian author non-byline.; Bynum-Bain Grantley author non-byline.; Kim Monica author non-byline.; Mendiguren Carolina author non-byline.; Huang Xiwen author non-byline.; Smith Monika author non-byline.; Eberhart Zrenner author non-byline.; Nasser Fadi author non-byline.; Hahn Gesa author non-byline.;
• Is Part Of: British journal of ophthalmology. Volume 103:Issue 3(2019)
• Page Start: 390
• Page End: 397
• Publication Date: 2018-06-20
• Subjects: genetics -- macula -- retina; Ophthalmology -- Periodicals; 617.7
• DOI: 10.1136/bjophthalmol-2018-312064
• Languages: English
• ISSNs: 0007-1161

Abstract

Abstract : Background/aims: To describe the genetic characteristics of the cohort enrolled in the international multicentre progression of Stargardt disease 1 (STGD1) studies (ProgStar) and to determine geographic differences based on the allele frequency. Methods: 345 participants with a clinical diagnosis of STGD1 and harbouring at least one disease-causing ABCA4 variant were enrolled from 9 centres in the USA and Europe. All variants were reviewed and in silico analysis was performed including allele frequency in public databases and pathogenicity predictions. Participants with multiple likely pathogenic variants were classified into four national subgroups (USA, UK, France, Germany), with subsequent comparison analysis of the allele frequency for each prevalent allele. Results: 211 likely pathogenic variants were identified in the total cohort, including missense (63%), splice site alteration (18%), stop (9%) and others. 50 variants were novel. Exclusively missense variants were detected in 139 (50%) of 279 patients with multiple pathogenic variants. The three most prevalent variants of these patients with multiple pathogenic variants were p.G1961E (15%), p.G863A (7%) and c.5461-10 T>C (5%). Subgroup analysis revealed a statistically significant difference between the four recruiting nations in the allele frequency of nine variants. Conclusions: There is a large spectrum of ABCA4 sequence variants, including 50 novel variants, in a well-characterised cohort thereby further adding to the unique allelic heterogeneity in STGD1. Approximately half of the cohort harbours missense variants only, indicating a relatively mild phenotype of the ProgStar cohort. There are significant differences in allele frequencies between nations, although the three most prevalent variants are shared as frequent variants.