HGNC Approved Gene Symbol: PLA2G5
SNOMEDCT: 770434009;
Cytogenetic location: 1p36.13 Genomic coordinates (GRCh38): 1:20,028,408-20,091,911 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 1p36.13 | [Fleck retina, familial benign] | 228980 | Autosomal recessive | 3 |
Chen et al. (1994) reported the cloning of a cDNA predicted to encode a 118-amino acid mature peptide with a 20-residue leader peptide. It is a member of the phospholipase A2 gene family. Because the protein lacks one of the 7 disulfide bridges found in related PLA2 genes it was classified as a member of a new group of phospholipases A2, designated Group V (Group IIA includes PLA2G2A (172411); Group IIC includes PLA2G2C). Northern blots showed a 1.2-kb transcript in heart and, at lower levels, in lung. Multiple putative transcripts were also observed in placenta.
By immunohistochemical staining of a donor eye from an 87-year-old man, Sergouniotis et al. (2011) demonstrated localization of group V phospholipase A2 predominantly in the inner and outer plexiform layers.
Tischfield et al. (1996) used in situ hybridization to show that PLA2G2A, PLA2G5, and PLA2G2C all mapped to 1p36-p34. Failure to find an exon present in the rodent homologs or transcripts in the expected tissues led the authors to conclude that PLA2G2C may be a pseudogene. The homologous mouse loci were shown to be tightly linked to the distal region of mouse chromosome 4.
Chen et al. (1994) demonstrated that when the cDNA was expressed in human 293 cells, PLA2 activity was observed in the culture medium. The conditioned medium hydrolyzed the phospholipids of oleate-labeled E. coli. In assays involving individual substrates, L-alpha-1-palmitoyl-2-oleoyl phosphatidylcholine was hydrolyzed most efficiently.
Using a combination of homozygosity mapping and exome sequencing in a consanguineous South Asian family in which 3 sibs had benign fleck retina (FRFB; 228980), Sergouniotis et al. (2011) identified a homozygous missense mutation in the PLA2G5 gene (601192.0001) that segregated with disease in the family. Sequencing of PLA2G5 in 4 unrelated individuals with benign fleck retina revealed homozygous or compound heterozygous mutations in 3 of the 4 affected individuals (601192.0001-601192.0005). Optical coherence tomography and fundus autofluorescence findings suggested that group V phospholipase A2 plays a role in phagocytosis of photoreceptor outer-segment discs by the retinal pigment epithelium.
In 3 affected sibs from a consanguineous family with benign fleck retina (FRFB; 228980), Sergouniotis et al. (2011) identified homozygosity for a 133G-T transversion in exon 3 of the PLA2G5 gene, resulting in a gly45-to-cys (G45C) substitution at a highly conserved residue. The mutation was not detected in a database of 224 control exomes from patients without a diagnosis of ophthalmic disease.
In a 12-year-old Indian boy with benign fleck retina (228980), previously studied by Audo et al. (2007), Sergouniotis et al. (2011) identified homozygosity for a 185G-A transition in exon 3 of the PLA2G5 gene, resulting in a trp62-to-ter (W62X) substitution. The mutation was not detected in a database of 224 control exomes from patients without a diagnosis of ophthalmic disease.
In a 28-year-old Australian woman with benign fleck retina (228980), originally reported by Isaacs et al. (1996), Sergouniotis et al. (2011) identified compound heterozygosity for a 145G-A transition in exon 3 of the PLA2G5 gene, resulting in a gly49-to-ser (G49S) substitution at a highly conserved residue, and a 157C-T transition in exon 3, resulting in an arg53-to-ter (R53X; 601192.0004) substitution. Neither mutation was detected in a database of 224 control exomes from patients without a diagnosis of ophthalmic disease.
For discussion of the arg53-to-ter (R53X) mutation in the PLA2G5 gene that was found in compound heterozygous state in a patient with benign fleck retina (228980) by Sergouniotis et al. (2011), see 601192.0003.
In a 39-year-old woman with benign fleck retina (228980), Sergouniotis et al. (2011) identified compound heterozygosity for a 1-bp deletion (383delA) in exon 5 of the PLA2G5 gene, predicted to result in a frameshift and premature termination codon, and the G45C missense mutation (601192.0001). Neither mutation was detected in a database of 224 control exomes from patients without a diagnosis of ophthalmic disease.
Audo, I., Tsang, S. H., Fu, A. D., Barnes, J. A., Holder, G. E., Moore, A. T. Autofluorescence imaging in a case of benign familial fleck retina. Arch. Ophthal. 125: 714-715, 2007. [PubMed: 17502520] [Full Text: https://doi.org/10.1001/archopht.125.5.714]
Chen, J., Engle, S. J., Seilhamer, J. J., Tischfield, J. A. Cloning and recombinant expression of a novel human low molecular weight Ca(2+)-dependent phospholipase A2. J. Biol. Chem. 269: 2365-2368, 1994. [PubMed: 8300559]
Isaacs, T. W., McAllister, I. L., Wade, M. S. Benign fleck retina. (Letter) Brit. J. Ophthal. 80: 267-269, 1996. [PubMed: 8703867] [Full Text: https://doi.org/10.1136/bjo.80.3.267]
Sergouniotis, P. I., Davidson, A. E., MacKay, D. S., Lenassi, E., Li, Z., Robson, A. G., Yang, X., Kam, J. H., Isaacs, T. W., Holder, G. E., Jeffery, G., Beck, J. A., Moore, A. T., Plagnol, V., Webster, A. R. Biallelic mutations in PLA2G5, encoding group V phospholipase A2, cause benign fleck retina. Am. J. Hum. Genet. 89: 782-791, 2011. [PubMed: 22137173] [Full Text: https://doi.org/10.1016/j.ajhg.2011.11.004]
Tischfield, J. A., Xia, Y.-R., Shih, D. M., Klisak, I., Chen, J., Engle, S. J., Siakotos, A. N., Winstead, M. V., Seilhamer, J. J., Allamand, V., Gyapay, G., Lusis, A. J. Low molecular weight, calcium-dependent phospholipase A(2) genes are linked and map to homologous chromosome regions in mouse and human. Genomics 32: 328-333, 1996. [PubMed: 8838795] [Full Text: https://doi.org/10.1006/geno.1996.0126]