Mutations in PNPLA6 are linked to photoreceptor degeneration and various forms of childhood blindness
Male
0301 basic medicine
Molecular Sequence Data
Retinal Degeneration
Blindness
R1
Retina
Pedigree
Mice, Inbred C57BL
Mice
03 medical and health sciences
Phenotype
Microscopy, Fluorescence
Phospholipases
Child, Preschool
Mutation
Animals
Humans
Drosophila
Female
Amino Acid Sequence
Child
Phospholipids
DOI:
10.1038/ncomms6614
Publication Date:
2015-01-09T14:18:24Z
AUTHORS (42)
ABSTRACT
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.
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CITATIONS (78)
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