The pathogenicity of SLC38A8 in five families with foveal hypoplasia and congenital nystagmus

Chen Weiner*, Idan Hecht, Ygal Rotenstreich, Sharon Guttman, Lior Or, Yair Morad, Guy Shapira, Noam Shomron, Eran Pras

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


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.

Original languageEnglish
Article number107958
JournalExperimental Eye Research
StatePublished - Apr 2020


FundersFunder number
Claire and Amedee Maratier Institute for the Study of Blindness
Consortium for Mapping Retinal Degeneration Disorders in IsraelBR-GE-0214-0639-TECH, BR-GE-0518-0734-TECH
Sackler Faculty of Medicine
Sackler Faculty of Medicine, Tel Aviv University
Tel-Aviv University
Foundation Fighting Blindness3-12583
Tel Aviv University
Claire and Amédée Maratier Institute for the Study of Blindness and Visual Disorders, Tel Aviv University32003197000, 32003125000
Ministry of Health, State of Israel


    • FHONDA syndrome
    • FVH2
    • Foveal hypoplasia
    • Karaite jews
    • SLC38A8


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