Chen Weiner1, Idan Hecht2, Ygal Rotenstreich3, Sharon Guttman2, Lior Or2, Yair Morad2, Guy Shapira4, Noam Shomron5, Eran Pras6. 1. Matlow's Ophthalmo-genetic Laboratory, Department of Ophthalmology, Shamir Medical Center (formerly Assaf Harofeh Medical Center), Zerifin, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: w24369@gmail.com. 2. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Ophthalmology, Shamir Medical Center, (formerly Assaf Harofeh Medical Center), Zerifin, Israel. 3. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Electrophysiology Clinic and Retinal Research Laboratory, Goldschleger Eye Institute, Sheba Medical Center, Israel. 4. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 5. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel; Edmond J. Safra Center of Bioinformatics, Tel Aviv University, Tel Aviv, Israel. 6. Matlow's Ophthalmo-genetic Laboratory, Department of Ophthalmology, Shamir Medical Center (formerly Assaf Harofeh Medical Center), Zerifin, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Ophthalmology, Shamir Medical Center, (formerly Assaf Harofeh Medical Center), Zerifin, Israel.
Abstract
PURPOSE: A recently described subtype of foveal hypoplasia with congenital nystagmus and optic-nerve-decussation defects was found to be associated with mutations in the SLC38A8 gene. The aim of this study is to advance the clinical and molecular knowledge of SLC38A8 gene mutations. METHODS: Five Israeli families with congenital foveal hypoplasia were studied, two of Karait Jewish origins and three of Indian Jewish origins. Subjects underwent a comprehensive ophthalmic examination including retinal photography and ocular coherence tomography. Molecular analysis including whole exome sequencing and screening of the SLC38A8 gene for specific disease-causing variants was performed. RESULTS: Eight affected individuals were identified, all had congenital nystagmus and all but one had hypoplastic foveal pits. Anterior segment dysgenesis was observed in only one patient, one had evidence of developmental delay and another displayed early age-related macular degeneration (AMD). Molecular analysis revealed a recently described homozygous mutation, c.95T > G; p.Ile32Ser, in two families of Jewish Indian descent, and the same mutation in two families of Karaite Jewish descent. In a patient with only one pathogenic mutation (c.95T > G; p.Ile32Ser), a possible partial clinical expression of the disorder was seen. One patient of Jewish Indian descent was found to be compound heterozygous for c.95T > G; p.Ile32Ser and a novel mutation c.490_491delCT; p.L164Vfs*41. CONCLUSIONS: In five unrelated families with congenital nystagmus and foveal hypoplasia, mutations in the SLC38A8 gene were identified. Possible partial expression in a heterozygous patient was observed and novel potential disease-related phenotypes were identified including early-onset AMD and developmental delay. A novel mutation was also identified and a similar mutation in both Indian and Karaite Jewish ethnicities could be suggestive for common ancestry.
PURPOSE: A recently described subtype of foveal hypoplasia with congenital nystagmus and optic-nerve-decussation defects was found to be associated with mutations in the SLC38A8 gene. The aim of this study is to advance the clinical and molecular knowledge of SLC38A8 gene mutations. METHODS: Five Israeli families with congenital foveal hypoplasia were studied, two of Karait Jewish origins and three of Indian Jewish origins. Subjects underwent a comprehensive ophthalmic examination including retinal photography and ocular coherence tomography. Molecular analysis including whole exome sequencing and screening of the SLC38A8 gene for specific disease-causing variants was performed. RESULTS: Eight affected individuals were identified, all had congenital nystagmus and all but one had hypoplastic foveal pits. Anterior segment dysgenesis was observed in only one patient, one had evidence of developmental delay and another displayed early age-related macular degeneration (AMD). Molecular analysis revealed a recently described homozygous mutation, c.95T > G; p.Ile32Ser, in two families of Jewish Indian descent, and the same mutation in two families of Karaite Jewish descent. In a patient with only one pathogenic mutation (c.95T > G; p.Ile32Ser), a possible partial clinical expression of the disorder was seen. One patient of Jewish Indian descent was found to be compound heterozygous for c.95T > G; p.Ile32Ser and a novel mutation c.490_491delCT; p.L164Vfs*41. CONCLUSIONS: In five unrelated families with congenital nystagmus and foveal hypoplasia, mutations in the SLC38A8 gene were identified. Possible partial expression in a heterozygous patient was observed and novel potential disease-related phenotypes were identified including early-onset AMD and developmental delay. A novel mutation was also identified and a similar mutation in both Indian and Karaite Jewish ethnicities could be suggestive for common ancestry.
Authors: Elena R Schiff; Vijay K Tailor; Hwei Wuen Chan; Maria Theodorou; Andrew R Webster; Mariya Moosajee Journal: Int J Mol Sci Date: 2021-01-24 Impact factor: 5.923
Authors: Charlotte C Kruijt; Libe Gradstein; Arthur A Bergen; Ralph J Florijn; Benoit Arveiler; Eulalie Lasseaux; Xavier Zanlonghi; Laura Bagdonaite-Bejarano; Anne B Fulton; Claudia Yahalom; Anat Blumenfeld; Yonatan Perez; Ohad S Birk; Gerard C de Wit; Nicoline E Schalij-Delfos; Maria M van Genderen Journal: Invest Ophthalmol Vis Sci Date: 2022-01-03 Impact factor: 4.799