title: Recessive mutations in SLC38A8 cause foveal hypoplasia and optic nerve misrouting without albinism.
abstract: Foveal hypoplasia and optic nerve misrouting are developmental defects of the visual pathway and only co-occur in connection with albinism; to date, they have only been associated with defects in the melanin-biosynthesis pathway. Here, we report that these defects can occur independently of albinism in people with recessive mutations in the putative glutamine transporter gene SLC38A8. Nine different mutations were identified in seven Asian and European families. Using morpholino-mediated ablation of Slc38a8 in medaka fish, we confirmed that pigmentation is unaffected by loss of SLC38A8. Furthermore, by undertaking an association study with SNPs at the SLC38A8 locus, we showed that common variants within this gene modestly affect foveal thickness in the general population. This study reveals a melanin-independent component underpinning the development of the visual pathway that requires a functional role for SLC38A8.
authors.affiliation: Leeds Institute of Molecular Medicine, University of Leeds, Leeds, West Yorkshire LS9 7TF, UK.
authors.forename: James A
authors.initials: JA
authors.lastname: Poulter
authors.forename: Musallam
authors.initials: M
authors.lastname: Al-Araimi
authors.forename: Ivan
authors.initials: I
authors.lastname: Conte
authors.forename: Maria M
authors.initials: MM
authors.lastname: van Genderen
authors.forename: Eamonn
authors.initials: E
authors.lastname: Sheridan
authors.forename: Ian M
authors.initials: IM
authors.lastname: Carr
authors.forename: David A
authors.initials: DA
authors.lastname: Parry
authors.forename: Mike
authors.initials: M
authors.lastname: Shires
authors.forename: Sabrina
authors.initials: S
authors.lastname: Carrella
authors.forename: John
authors.initials: J
authors.lastname: Bradbury
authors.forename: Kamron
authors.initials: K
authors.lastname: Khan
authors.forename: Phillis
authors.initials: P
authors.lastname: Lakeman
authors.forename: Panagiotis I
authors.initials: PI
authors.lastname: Sergouniotis
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Webster
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Moore
authors.forename: Bishwanath
authors.initials: B
authors.lastname: Pal
authors.forename: Moin D
authors.initials: MD
authors.lastname: Mohamed
authors.forename: Anandula
authors.initials: A
authors.lastname: Venkataramana
authors.forename: Vedam
authors.initials: V
authors.lastname: Ramprasad
authors.forename: Rohit
authors.initials: R
authors.lastname: Shetty
authors.forename: Murugan
authors.initials: M
authors.lastname: Saktivel
authors.forename: Govindasamy
authors.initials: G
authors.lastname: Kumaramanickavel
authors.forename: Alex
authors.initials: A
authors.lastname: Tan
authors.forename: David A
authors.initials: DA
authors.lastname: Mackey
authors.forename: Alex W
authors.initials: AW
authors.lastname: Hewitt
authors.forename: Sandro
authors.initials: S
authors.lastname: Banfi
authors.forename: Manir
authors.initials: M
authors.lastname: Ali
authors.forename: Chris F
authors.initials: CF
authors.lastname: Inglehearn
authors.forename: Carmel
authors.initials: C
authors.lastname: Toomes
mesh_terms: D000417:Albinism; D026921:Amino Acid Transport Systems, Neutral / Q000235:genetics*; D000818:Animals; D002648:Child; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005260:Female; D005584:Fovea Centralis / Q000002:abnormalities*; D005808:Genes, Recessive; D006720:Homozygote; D006801:Humans; D008297:Male; D009154:Mutation; D009900:Optic Nerve / Q000503:physiopathology*; D010375:Pedigree; D010641:Phenotype; D013577:Syndrome
chemical_list: D026921:Amino Acid Transport Systems, Neutral; C579438:Slc38a8 protein, human