Independent COL5A1 Variants in Cats with Ehlers-Danlos Syndrome.

We investigated four cats with similar clinical skin-related signs strongly suggestive of Ehlers-Danlos syndrome (EDS). Cases no. 1 and 4 were unrelated and the remaining two cases, no. 2 and 3, were reportedly siblings. Histopathological changes were characterized by severely altered dermal collagen fibers. Transmission electron microscopy in one case demonstrated abnormalities in the collagen fibril organization and structure. The genomes of the two unrelated affected cats and one of the affected siblings were sequenced and individually compared to 54 feline control genomes. We searched for private protein changing variants in known human EDS candidate genes and identified three independent heterozygous COL5A1 variants. COL5A1 is a well-characterized candidate gene for classical EDS. It encodes the proα1 chain of type V collagen, which is needed for correct collagen fibril formation and the integrity of the skin. The identified variants in COL5A1 are c.112_118+15del or r.spl?, c.3514A>T or p.(Lys1172*), and c.3066del or p.(Gly1023Valfs*50) for cases no. 1, 2&3, and 4, respectively. They presumably all lead to nonsense-mediated mRNA decay, which results in haploinsufficiency of COL5A1 and causes the alterations of the connective tissue. The whole genome sequencing approach used in this study enables a refinement of the diagnosis for the affected cats as classical EDS. It further illustrates the potential of such experiments as a precision medicine approach in animals with inherited diseases.

First case of a natural infection in a domestic cat (Felis catus) with the canid heart worm Angiostrongylus vasorum.

Cardiopulmonary nematodes in cats include different parasite species affecting feline lungs and the heart, with the metastrongyloid Aelurostrongylus abstrusus being the most frequent feline lungworm worldwide. The present case report describes an 11-month-old male neutered European short hair cat which presented with generalised subcutaneous oedema and pleural and peritoneal effusions. According to clinical examination, abdominal imaging and laboratory analyses, a tentative diagnosis of severe glomerulopathy with massive proteinuria was made. Due to worsening of the clinical signs despite therapeutic interventions and a poor prognosis, the cat was euthanised. Necropsy and histological examinations revealed severe bilateral collagenofibrotic glomerulopathy, generalised oedema and a focal verminous pneumonia with thrombosis in arterial lung vessels containing nematode cross sections. A serum sample was tested for the presence of antibodies against the cat lungworm A. abstrusus, resulting negative. Genetic analyses confirmed the presence of nematode DNA; after exclusion of common lung and heart parasites occurring in cats, DNA of the canid heart worm nematode Angiostrongylus vasorum was identified. This is the first description of a naturally occurring infection with A. vasorum in a cat. Previous experimental studies demonstrated the development of adult male and female A. vasorum worms containing eggs in cats, but no larval excretion in the faeces. Although cats did not become patent, A. vasorum infections were clinically relevant. As A. abstrusus and A. vasorum are both gastropod transmitted nematodes, they may share the same intermediate hosts within overlapping areas. In addition, especially chronic A. abstrusus infected cats become non-patent and do not excrete L1. Considering that patent A. vasorum infections are widespread in the dog and fox population in Switzerland (and several other countries) but are apparently not patent in cats, we cannot exclude that infections with A. vasorum may occur more frequently than expected.