Miriam Bauwens, Alejandro Garanto, Riccardo Sangermano, Sarah Naessens, Nicole Weisschuh, Julie De Zaeytijd, Mubeen Khan, Françoise Sadler, Irina Balikova, Caroline Van Cauwenbergh, Toon Rosseel, Jim Bauwens, Kim De Leeneer, Sarah De Jaegere, Thalia Van Laethem, Meindert De Vries, Keren Carss, Gavin Arno, Ana Fakin, Andrew R Webster, Thomy J L de Ravel de l'Argentière, Yves Sznajer, Marnik Vuylsteke, Susanne Kohl, Bernd Wissinger, Timothy Cherry, Rob W J Collin, Frans P M Cremers, Bart P Leroy, Elfride De Baere
PURPOSE: ABCA4-associated disease, a recessive retinal dystrophy, is hallmarked by a large proportion of patients with only one pathogenic ABCA4 variant, suggestive for missing heritability. METHODS: By locus-specific analysis of ABCA4, combined with extensive functional studies, we aimed to unravel the missing alleles in a cohort of 67 patients (p), with one (p = 64) or no (p = 3) identified coding pathogenic variants of ABCA4. RESULTS: We identified eight pathogenic (deep-)intronic ABCA4 splice variants, of which five are novel and six structural variants, four of which are novel, including two duplications...
January 23, 2019: Genetics in Medicine: Official Journal of the American College of Medical Genetics