Simon, Rebecca; Kiener, Sarah; Thom, Nina; Schäfer, Laura; Müller, Janina; Schlohsarczyk, Elfi K; Gärtner, Ulrich; Herden, Christiane; Leeb, Tosso; Lühken, Gesine (2023). Identification of an ADAMTS2 frameshift variant in a cat family with Ehlers-Danlos syndrome. G3 Genes Genomes Genetics, 13(9) Genetics Society of America 10.1093/g3journal/jkad152
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We investigated four European domestic shorthair kittens with skin lesions consistent with the dermatosparaxis type of the Ehlers-Danlos syndrome (EDS), a connective tissue disorder. The kittens were sired by the same tomcat, but were born by three different mothers. The kittens had easily torn skin resulting in non-healing skin wounds. Both clinically and histologically, the skin showed thin epidermis in addition to inflammatory changes. Changes in collagen fibers were visible in electron micrographs. The complete genome of an affected kitten was sequenced. A one base pair duplication leading to a frameshift in the candidate gene ADAMTS2 was identified, p.(Ser235fs*3). All four affected cats carried the frameshift duplication in a homozygous state. Genotypes at this variant showed perfect co-segregation with the autosomal recessive EDS phenotype in the available family. The mutant allele did not occur in 48 unrelated control cats. ADAMTS2 loss-of-function variants cause autosomal recessive forms of EDS in humans, mice, dogs, cattle and sheep. The available evidence from our investigation together with the functional knowledge on ADAMTS2 in other species allow to classify the identified ADAMTS2 variant as pathogenic and most likely causative variant for the observed EDS.
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