Recessive mutations in SLC38a8 cause foveal hypoplasia and optic nerve misrouting without albinism

James A. Poulter, Musallam Al-Araimi, Ivan Conte, Maria M. Van Genderen, Eamonn Sheridan, Ian M. Carr, David A. Parry, Mike Shires, Sabrina Carrella, John Bradbury, Kamron Khan, Phillis Lakeman, Panagiotis I. Sergouniotis, Andrew R. Webster, Anthony T. Moore, Bishwanath Pal, Moin D. Mohamed, Anandula Venkataramana, Vedam Ramprasad, Rohit ShettyMurugan Saktivel, Govindasamy Kumaramanickavel, Alex Tan, David A. Mackey, Alex W. Hewitt, Sandro Banfi, Manir Ali, Chris F. Inglehearn*, Carmel Toomes

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1143-1150
Number of pages8
JournalAmerican Journal of Human Genetics
Volume93
Issue number6
DOIs
Publication statusPublished - 5 Dec 2013

Fingerprint

Dive into the research topics of 'Recessive mutations in SLC38a8 cause foveal hypoplasia and optic nerve misrouting without albinism'. Together they form a unique fingerprint.

Cite this