Exclusion of previously described variant in LTBP2 for primary glaucoma in Australian Burmese cats

Abstract

Glaucoma is a diverse group of progressive neurodegenerative eye disorders that can lead to irreversible blindness (Davis et al., 2016; Maggio, 2015; Weinreb et al., 2014). Based on the underlying aetiology, glaucoma can be classified as either primary or secondary and within primary further categorised as open or closed angle. Both forms result in an increased intraocular pressure (IOP), and while secondary glaucoma is characterised by an increase in IOP due to pathological process such as inflammation, primary glaucoma lacks these distinguishable pathologies. Being one of the most common heritable disorders in humans, 112 genetic loci and variants in 74 genes have been identified as being associated with primary glaucoma to date (Gao et al., 2018; Khawaja et al., 2018; MacGregor et al., 2018; Wang et al., 2017, 2018). While less common, primary glaucoma has been described in dogs and cats (Hampson et al., 2002; Martin & Wyman, 1978; Miller & Bentley, 2015; Schallek et al., 2012), and, although rarely observed in cats, a breed predisposition has been reported in Burmese, Siamese, and Persian cats (Dietrich, 2005; Glaze, 2005).

To date, only one variant in the Latent Transforming Growth Factor-β Binding Protein 2 (LTBP2) gene has been associated with primary glaucoma in domestic cats (Kuehn et al., 2016). The aim of this study was to assess for the presence of the previously described variant in Australian Burmese cats clinically diagnosed with primary glaucoma.

EDTA-stabilised whole blood from 10 Australian Burmese cats diagnosed with primary glaucoma at a specialist animal eye hospital in Sydney were collected and genomic DNA isolated using a standard phenol–chloroform extraction method. Genotypes for the LTBP2 variant were determined by PCR and direct sequencing of PCR products as described before (Gao et al., 2018). Sequence data were analysed using Sequencher 5.4.6 (GeneCodes) and compared to the feline LTBP2 reference sequence (XM_023255858.2) according to FelCat9.

Sequence data analysis demonstrated that none of the 10 affected Burmese cats carried the previously described 4-bp insertion in the LTBP2 gene (g.121929604_121929607insCCTC; according to FelCat9) and that all cases were homozygous for the wild-type allele at this position. As none of the cases investigated carried the previously described variant in LTBP2 (Kuehn et al., 2016), this variant can be excluded from being responsible for primary glaucoma in the investigated Burmese cats. Considering that the previously described variant in LTBP2 has been identified in Siamese cats, another yet unknown genetic variant may be responsible for the observed phenotype in the Burmese cat. While LTBP2 still represents a good candidate gene for further investigation, the genetically heterogeneous nature of primary glaucoma in humans and dogs suggests that a variant in a different gene might be associated with primary glaucoma in Burmese cats (Ali et al., 2009; Gao et al., 2018; Khawaja et al., 2018; Kuchtey et al., 2011, 2013; MacGregor et al., 2018; Suri et al., 2018; Zukerman et al., 2021). As it was not possible to obtain pedigree information for the cases investigated, the exact mode of inheritance of primary glaucoma in the Australian Burmese cat population is yet to be determined. Considering that primary glaucoma in humans commonly follows an autosomal recessive inheritance pattern and that similar findings have been made in the dog, it is likely that this will also be the case for the cat (Asefa et al., 2019; Cascella et al., 2015; Kuchtey et al., 2011, 2013; Sarfarazi et al., 2003; Zukerman et al., 2021).

The authors declare that they have no competing interests.