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

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. På Istoupilová, K. HodaÅ ová, L. Piherová, L. KuchaÅ, A. Baxová, R. Chen, O. G.P. BarsottiniA. Pyle, H. Griffin, M. Splitt, J. Sallum, J. L. Tolmie, J. R. Sampson, P. Chinnery, E. Banin, D. Sharon, S. Dutta, R. Grebler, C. Helfrich-Foerster, J. L. Pedroso, D. Kretzschmar, M. Cayouette, R. K. Koenekoop, Kym Boycott, Alex MacKenzie, Michael Brudno, Dennis Bulman, David Dyment

Research output: Contribution to journalArticlepeer-review

71 Scopus citations


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 the target of toxic organophosphates that induce human paralysis due to severe axonopathy of large neurons. Mutations in PNPLA6 also cause human spastic paraplegia characterized by motor neuron degeneration. Here we identify PNPLA6 mutations in childhood blindness in seven families with retinal degeneration, including Leber congenital amaurosis and Oliver McFarlane syndrome. PNPLA6 localizes mostly at the inner segment plasma membrane in photoreceptors and mutations in Drosophila PNPLA6 lead to photoreceptor cell death. We also report that lysophosphatidylcholine and lysophosphatidic acid levels are elevated in mutant Drosophila. These findings show a role for PNPLA6 in photoreceptor survival and identify phospholipid metabolism as a potential therapeutic target for some forms of blindness.

Original languageEnglish (US)
Article number5614
JournalNature communications
StatePublished - Jan 8 2015

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy


Dive into the research topics of 'Mutations in PNPLA6 are linked to photoreceptor degeneration and various forms of childhood blindness'. Together they form a unique fingerprint.

Cite this