LTBP3 Frameshift Variant in British Shorthair Cats with Complex Skeletal Dysplasia

Rudd Garces, Gabriela; Knebel, Anna; Hülskötter, Kirsten; Jagannathan, Vidhya; Störk, Theresa; Hewicker-Trautwein, Marion; Leeb, Tosso; Volk, Holger A. (2021). LTBP3 Frameshift Variant in British Shorthair Cats with Complex Skeletal Dysplasia. Genes, 12(12), p. 1923. MDPI 10.3390/genes12121923

Preview

Text Rudd_Garces_2021_Genes_12_1923.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (752kB) | Preview

We investigated a highly inbred family of British Shorthair cats in which two offspring were affected by deteriorating paraparesis due to complex skeletal malformations. Radiographs of both affected kittens revealed vertebral deformations with marked stenosis of the vertebral canal from T11 to L3. Additionally, compression of the spinal cord, cerebellar herniation, coprostasis and hypogangliosis were found. The pedigree suggested monogenic autosomal recessive inheritance of the trait. We sequenced the genome of an affected kitten and compared the data to 62 control genomes. This search yielded 55 private protein-changing variants of which only one was located in a likely functional candidate gene, LTBP3, encoding latent transforming growth factor β binding protein 3. This variant, c.158delG or p.(Gly53Alafs*16), represents a 1 bp frameshift deletion predicted to truncate 95% of the open reading frame. LTBP3 is a known key regulator of transforming growth factor β (TGF-β) and is involved in bone morphogenesis and remodeling. Genotypes at the LTBP3:c.158delG variant perfectly co-segregated with the phenotype in the investigated family. The available experimental data together with current knowledge on LTBP3 variants and their functional impact in human patients and mice suggest LTBP3:c.158delG as a candidate causative variant for the observed skeletal malformations in British Shorthair cats. To the best of our knowledge, this study represents the first report of LTBP3-related complex skeletal dysplasia in domestic animals

Interest & Impact

Downloads

100 since deposited on 01 Dec 2021
28 in the past 12 months

Citations

5 Citations in Web of Science ®
6 Citations in Scopus

Search

in Google Scholar™

Services

Actions (login required)

Edit item

Actions (login required)

Edit item