Biallelic mutations in PLA2G5, encoding group V phospholipase A2, cause benign fleck retina
Panagiotis I Sergouniotis1, Alice E Davidson, Donna S Mackay
1Institute of Ophthalmology, University College London, London, UK.
American Journal of Human Genetics
|December 6, 2011
Summary
Benign fleck retina is linked to mutations in the PLA2G5 gene, which encodes group V phospholipase A(2). This discovery sheds light on the gene
Area of Science:
- Ophthalmology and Genetics
- Retinal Diseases
- Molecular Biology
Background:
- Flecked-retina syndromes are a group of disorders characterized by yellow-white retinal lesions.
- Benign fleck retina is one such disorder, with varying distributions and configurations of these lesions.
- The genetic basis for benign fleck retina has remained largely uncharacterized.
Purpose of the Study:
- To identify the genetic cause of benign fleck retina in affected individuals.
- To investigate the role of the identified gene in retinal function.
- To understand the protein localization and potential function within the retina.
Main Methods:
- Homozygosity mapping and exome sequencing were employed to identify genetic variants.
- PLA2G5 gene variants were screened in additional patients with benign fleck retina.
- Fundoscopic, optical coherence tomography, fundus autofluorescence, and immunohistochemical analyses were performed.
Main Results:
- A homozygous missense mutation (c.133G>T, p.Gly45Cys) in the PLA2G5 gene was identified in three siblings with benign fleck retina.
- Biallelic PLA2G5 variants were found in three of four additional unrelated patients with benign fleck retina.
- PLA2G5 variants were not found in control populations, and the protein was localized to the inner and outer plexiform layers.
Conclusions:
- Mutations in the PLA2G5 gene are a cause of benign fleck retina.
- Group V phospholipase A(2) likely plays a role in photoreceptor outer-segment disc phagocytosis by the retinal pigment epithelium.
- The identified PLA2G5 variants and protein localization provide new insights into the pathogenesis of flecked-retina syndromes.
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