Mutations in PNPLA6 are linked to photoreceptor degeneration and various forms of childhood blindness

• DOI: 10.1038/ncomms6614
• Publication Date: 2015-01-09T14:18:24Z
• Authors: S. Kmoch; J. Majewski; V. Ramamurthy; S. Cao; S. Fahiminiya; H. Ren; I. M. MacDonald; I. Lopez; V. Sun; V. Keser; A. Khan; V. Stránecký; H. Hartmannová; A. Přistoupilová; K. Hodaňová; L. Piherová; L. Kuchař; A. Baxová; R. Chen; O. G. P. Barsottini; A. Pyle; H. Griffin; M. Splitt; J. Sallum; J. L. Tolmie; J. R. Sampson; P. Chinnery; ; Kym Boycott; Alex MacKenzie; Michael Brudno; Dennis Bulman; David Dyment; E. Banin; D. Sharon; S. Dutta; R. Grebler; C. Helfrich-Foerster; J. L. Pedroso; D. Kretzschmar; M. Cayouette; R. K. Koenekoop
• Keywords: Hereditary Spastic Paraplegia; Photoreceptor cell; Degeneration (medical)

Blindness due to retinal degeneration affects millions of people worldwide, but many disease-causing mutations remain unknown. PNPLA6 encodes the patatin-like phospholipase domain containing protein 6, also known as neuropathy target esterase (NTE), which is toxic organophosphates that induce human paralysis severe axonopathy large neurons. Mutations in cause spastic paraplegia characterized by motor neuron degeneration. Here we identify childhood blindness seven families with degeneration, including Leber congenital amaurosis and Oliver McFarlane syndrome. localizes mostly at inner segment plasma membrane photoreceptors Drosophila lead photoreceptor cell death. We report lysophosphatidylcholine lysophosphatidic acid levels are elevated mutant Drosophila. These findings show a role for survival phospholipid metabolism potential therapeutic some forms blindness. authors link gene plays