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FH<\/jats:styled-content> is characterized by the absence of both the retinal foveal pit and avascular zone, but with preserved retinal architecture. SLC<\/jats:styled-content>38A8<\/jats:italic> encodes a sodium\u2010coupled neutral amino acid transporter with a preference for glutamate as a substrate. SLC<\/jats:styled-content>38A8 has been linked to FH<\/jats:styled-content>. Here, we describe a novel mutation to SLC<\/jats:styled-content>38A8<\/jats:italic> which causes FH<\/jats:styled-content>, and report the novel use of OCT<\/jats:styled-content>\u2010angiography to improve the precision of FH<\/jats:styled-content> diagnosis. More so, we used computational modeling to explore possible functional effects of known SLC<\/jats:styled-content>38A8 mutations.<\/jats:p><\/jats:sec>Methods<\/jats:title>Fundus autofluorescence, SD<\/jats:styled-content>\u2010OCT<\/jats:styled-content>, and OCT<\/jats:styled-content>\u2010angiography were used to make the clinical diagnosis. Whole\u2010exome sequencing led to the identification of a novel disease\u2010causing variant in SLC<\/jats:styled-content>38A8<\/jats:italic>. Computational modeling approaches were used to visualize known SLC<\/jats:styled-content>38A8 mutations, as well as to predict mutation effects on transporter structure and function.<\/jats:p><\/jats:sec>Results<\/jats:title>We identified a novel point mutation in SLC<\/jats:styled-content>38A8<\/jats:italic> that causes FH<\/jats:styled-content>. A conclusive diagnosis was made using OCT<\/jats:styled-content>\u2010angiography, which more clearly revealed retinal vasculature penetrating into the foveal region. Structural modeling of the channel showed the mutation was near previously published mutations, clustered on an extracellular loop. Our modeling also predicted that the mutation destabilizes the protein by altering the electrostatic potential within the channel pore.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Our results demonstrate a novel use for OCT<\/jats:styled-content>\u2010angiography in confirming FH<\/jats:styled-content>, and also uncover genotype\u2013phenotype correlations of FH<\/jats:styled-content>\u2010linked SLC<\/jats:styled-content>38A8<\/jats:italic> mutations.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.266","type":"journal-article","created":{"date-parts":[[2017,2,26]],"date-time":"2017-02-26T05:13:22Z","timestamp":1488086002000},"page":"202-209","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Structural modeling of a novel SLC<\/scp>38A8<\/i> mutation that causes foveal hypoplasia"],"prefix":"10.1002","volume":"5","author":[{"given":"Marcus A.","family":"Toral","sequence":"first","affiliation":[{"name":"Omics Laboratory University of Iowa Iowa City Iowa"},{"name":"Department of Ophthalmology and Visual Sciences University of Iowa Iowa City Iowa"},{"name":"Medical Scientist Training Program University of Iowa Iowa City Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Velez","sequence":"additional","affiliation":[{"name":"Omics Laboratory University of Iowa Iowa City Iowa"},{"name":"Department of Ophthalmology and Visual Sciences University of Iowa Iowa City Iowa"},{"name":"Medical Scientist Training Program University of Iowa Iowa City Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Boudreault","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology University of Montreal Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kellie A.","family":"Schaefer","sequence":"additional","affiliation":[{"name":"Omics Laboratory University of Iowa Iowa City Iowa"},{"name":"Department of Ophthalmology and Visual Sciences University of Iowa Iowa City Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology University of Montreal Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norman","family":"Saffra","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Maimonides Medical Center Brooklyn New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander G.","family":"Bassuk","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Iowa Iowa City Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen H.","family":"Tsang","sequence":"additional","affiliation":[{"name":"The Barbara & Donald Jonas Laboratory of Regenerative Medicine and Bernard & Shirlee Brown Glaucoma Laboratory Departments of Ophthalmology, Pathology & Cell Biology College of Physicians & Surgeons Columbia University New York City New York"},{"name":"Edward S. Harkness Eye Institute New York\u2010Presbyterian Hospital New York City New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinit B.","family":"Mahajan","sequence":"additional","affiliation":[{"name":"Omics Laboratory University of Iowa Iowa City Iowa"},{"name":"Department of Ophthalmology and Visual Sciences University of Iowa Iowa City Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,2,26]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471142905.hg0720s76"},{"key":"e_1_2_7_3_1","first-page":"2165","article-title":"A new recessively inherited disorder composed of foveal hypoplasia, optic nerve decussation defects and anterior segment dysgenesis maps to chromosome 16q23.3\u201024.1","volume":"19","author":"Al\u2010Araimi M.","year":"2013","journal-title":"Mol. 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