Compound heterozygosity for TNXB genetic variants in a mixed-breed dog with Ehlers-Danlos syndrome.

Bauer, Anina; de Lucia, M; Leuthard, Fabienne Nadja; Jagannathan, Vidya; Leeb, Tosso (2019). Compound heterozygosity for TNXB genetic variants in a mixed-breed dog with Ehlers-Danlos syndrome. Animal genetics, 50(5), pp. 546-549. Wiley 10.1111/age.12830

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The Ehlers-Danlos syndromes (EDSs) are a heterogeneous group of inherited connective tissue disorders characterized by skin hyperextensibility, joint hypermobility and tissue fragility. Inherited disorders similar to human EDS have been reported in different mammalian species. In the present study, we investigated a female mixed-breed dog with clinical signs of EDS. Whole-genome sequencing of the affected dog revealed two missense variants in the TNXB gene, encoding the extracellular matrix protein tenascin XB. In humans, TNXB genetic variants cause classical-like EDS or the milder hypermobile EDS. The affected dog was heterozygous at both identified variants. Each variant allele was transmitted from one of the case's parents, consistent with compound heterozygosity. Although one of the variant alleles, XM_003431680.3:c.2012G>A, p.(Ser671Asn), was private to the family of the affected dog and absent from whole-genome sequencing data of 599 control dogs, the second variant allele, XM_003431680.3:c.2900G>A, p.(Gly967Asp), is present at a low frequency in the Chihuahua and Poodle population. Given that TNXB is a functional candidate gene for EDS, we suggest that compound heterozygosity for the identified TNXB variants may have caused the EDS-like phenotype in the affected dog. Chihuahuas and Poodles should be monitored for EDS cases, which might confirm the hypothesized pathogenic effect of the segregating TNXB variant.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Institute of Genetics
05 Veterinary Medicine > Research Foci > DermFocus
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH)

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Bauer, Anina; Leuthard, Fabienne Nadja; Jagannathan, Vidya and Leeb, Tosso

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 590 Animals (Zoology)
600 Technology > 610 Medicine & health

ISSN:

0268-9146

Publisher:

Wiley

Language:

English

Submitter:

Tosso Leeb

Date Deposited:

04 Sep 2019 16:28

Last Modified:

26 Oct 2019 16:42

Publisher DOI:

10.1111/age.12830

PubMed ID:

31365140

Uncontrolled Keywords:

Canis lupus familiaris animal model connective tissue genodermatosis precision medicine skin whole-genome sequencing

BORIS DOI:

10.7892/boris.133009

URI:

https://boris.unibe.ch/id/eprint/133009

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