Biallelic mutations in PLA2G5, encoding group V phospholipase A2, cause benign fleck retina.

Abstract

Flecked-retina syndromes, including fundus flavimaculatus, fundus albipunctatus, and benign fleck retina, comprise a group of disorders with widespread or limited distribution of yellow-white retinal lesions of various sizes and configurations. Three siblings who have benign fleck retina and were born to consanguineous parents are the basis of this report. A combination of homozygosity mapping and exome sequencing helped to identify a homozygous missense mutation, c.133G>T (p.Gly45Cys), in PLA2G5, a gene encoding a secreted phospholipase (group V phospholipase A(2)). A screen of a further four unrelated individuals with benign fleck retina detected biallelic variants in the same gene in three patients. In contrast, no loss of function or common (minor-allele frequency>0.05%) nonsynonymous PLA2G5 variants have been previously reported (EVS, dbSNP, 1000 Genomes Project) or were detected in an internal database of 224 exomes (from subjects with adult onset neurodegenerative disease and without a diagnosis of ophthalmic disease). All seven affected individuals had fundoscopic features compatible with those previously described in benign fleck retina and no visual or electrophysiological deficits. No medical history of major illness was reported. Levels of low-density lipoprotein were mildly elevated in two patients. Optical coherence tomography and fundus autofluorescence findings suggest that group V phospholipase A(2) plays a role in the phagocytosis of photoreceptor outer-segment discs by the retinal pigment epithelium. Surprisingly, immunohistochemical staining of human retinal tissue revealed localization of the protein predominantly in the inner and outer plexiform layers.

• Authors: Panagiotis I Sergouniotis, Alice E Davidson, Donna S Mackay, Eva Lenassi, Zheng Li, Anthony G Robson, Xu Yang, Jaimie Hoh Kam, Timothy W Isaacs, Graham E Holder, Glen Jeffery, Jonathan A Beck, Anthony T Moore, Vincent Plagnol, Andrew R Webster
• Journal: American journal of human genetics (Am J Hum Genet) Vol. 89 Issue 6 Pg. 782-91 (Dec 09 2011) ISSN: 1537-6605 [Electronic] United States
• PMID: 22137173 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Chemical References

• Group V Phospholipases A2
• PLA2G5 protein, human

Topics

• Adult
• Aged, 80 and over
• Alternative Splicing
• Amino Acid Sequence
• Base Sequence
• Child
• Consanguinity
• Eye Abnormalities (genetics)
• Female
• Genetic Association Studies
• Group V Phospholipases A2 (genetics, metabolism)
• Homozygote
• Humans
• Male
• Molecular Sequence Data
• Mutation, Missense
• Pedigree
• Polymorphism, Single Nucleotide
• Protein Transport
• Retina (abnormalities, metabolism)