title: Isolated foveal hypoplasia with secondary nystagmus and low vision is associated with a homozygous SLC38A8 mutation.
abstract: Foveal hypoplasia, always accompanied by nystagmus, is found as part of the clinical spectrum of various eye disorders such as aniridia, albinism and achromatopsia. However, the molecular basis of isolated autosomal recessive foveal hypoplasia is yet unknown. Individuals of apparently unrelated non consanguineous Israeli families of Jewish Indian (Mumbai) ancestry presented with isolated foveal hypoplasia associated with congenital nystagmus and reduced visual acuity. Genome-wide homozygosity mapping followed by fine mapping defined a 830 Kb disease-associated locus (LOD score 3.5). Whole-exome sequencing identified a single missense mutation in the homozygosity region: c.95T>G, p.(Ile32Ser), in a conserved amino acid within the first predicted transmembrane domain of SLC38A8. The mutation fully segregated with the disease-associated phenotype, demonstrating an ∼10% carrier rate in Mumbai Jews. SLC38A8 encodes a putative sodium-dependent amino-acid/proton antiporter, which we showed to be expressed solely in the eye. Thus, a homozygous SLC38A8 mutation likely underlies isolated foveal hypoplasia.
authors.affiliation: The Morris Kahn Laboratory of Human Genetics at the National Institute of Biotechnology in the Negev, Ben-Gurion University, Beer-Sheva, Israel.
authors.forename: Yonatan
authors.initials: Y
authors.lastname: Perez
authors.affiliation: Department of Ophthalmology, Soroka Medical Center and Clalit Health Services, Faculty of Health Sciences, Ben-Gurion University, Beer-Sheva, Israel.
authors.forename: Libe
authors.initials: L
authors.lastname: Gradstein
authors.affiliation: Zussman Child Development Center, Soroka Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Hagit
authors.initials: H
authors.lastname: Flusser
authors.affiliation: The Morris Kahn Laboratory of Human Genetics at the National Institute of Biotechnology in the Negev, Ben-Gurion University, Beer-Sheva, Israel.
authors.forename: Barak
authors.initials: B
authors.lastname: Markus
authors.affiliation: The Morris Kahn Laboratory of Human Genetics at the National Institute of Biotechnology in the Negev, Ben-Gurion University, Beer-Sheva, Israel.
authors.forename: Idan
authors.initials: I
authors.lastname: Cohen
authors.affiliation: 1] The Morris Kahn Laboratory of Human Genetics at the National Institute of Biotechnology in the Negev, Ben-Gurion University, Beer-Sheva, Israel [2] Genetics Institute, Soroka Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Yshaia
authors.initials: Y
authors.lastname: Langer
authors.affiliation: Department of Ophthalmology, Soroka Medical Center and Clalit Health Services, Faculty of Health Sciences, Ben-Gurion University, Beer-Sheva, Israel.
authors.forename: Mira
authors.initials: M
authors.lastname: Marcus
authors.affiliation: Department of Ophthalmology, Soroka Medical Center and Clalit Health Services, Faculty of Health Sciences, Ben-Gurion University, Beer-Sheva, Israel.
authors.forename: Tova
authors.initials: T
authors.lastname: Lifshitz
authors.affiliation: The Morris Kahn Laboratory of Human Genetics at the National Institute of Biotechnology in the Negev, Ben-Gurion University, Beer-Sheva, Israel.
authors.forename: Rotem
authors.initials: R
authors.lastname: Kadir
authors.affiliation: 1] The Morris Kahn Laboratory of Human Genetics at the National Institute of Biotechnology in the Negev, Ben-Gurion University, Beer-Sheva, Israel [2] Genetics Institute, Soroka Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Ohad S
authors.initials: OS
authors.lastname: Birk
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D026921:Amino Acid Transport Systems, Neutral / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D015785:Eye Diseases, Hereditary / Q000150:complications* / Q000235:genetics*; D005260:Female; D005584:Fovea Centralis / Q000002:abnormalities*; D005786:Gene Expression Regulation; D008040:Genetic Linkage; D055106:Genome-Wide Association Study; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020417:Nystagmus, Congenital / Q000150:complications* / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D015354:Vision, Low / Q000209:etiology*; D055815:Young Adult
chemical_list: D026921:Amino Acid Transport Systems, Neutral; C579438:Slc38a8 protein, human
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