An IL17RA frameshift variant in a Holstein cattle family with psoriasis-like skin alterations and immunodeficiency

Häfliger, Irene M.; Sickinger, Marlene; Holsteg, Mark; Raeder, Leif M.; Henrich, Manfred; Marquardt, Siegfried; Drögemüller, Cord; Lühken, Gesine (2020). An IL17RA frameshift variant in a Holstein cattle family with psoriasis-like skin alterations and immunodeficiency. BMC genetics, 21(1) BioMed Central 10.1186/s12863-020-00860-4

[img]
Preview
Text
Häfliger_et_al_BMC-Genetics_2020.pdf - Published Version
Available under License Creative Commons: Attribution (CC-BY).

Download (12MB) | Preview

Skin lesions and dermatoses in cattle are often associated with infections due to bacteria, fungi or environmental risk factors. Dermatoses with genetic etiology have been described in cattle. Among these rare disorders, there are primary congenital dermatoses that are associated with inherited nutritional deficiencies, such as bovine hereditary zinc deficiency or zinc deficiency-like syndrome. This study presents three cases of Holstein cattle with congenital skin lesions observed on a single farm that resemble zinc deficiency-like syndrome. Close clinical and pathological examinations took place in two cases. Pedigree analysis indicated autosomal recessive inheritance and whole-genome sequencing of both affected calves was performed. The two calves showed retarded growth and suffered from severe ulcerative dermatitis with hyperkeratosis, alopecia furunculosis and subcutaneous abscess formation. Blood analysis showed correspondent leukocytosis with neutrophilia whereas minerals, macro- and micronutrients were within the reference ranges. Variant calling and filtering against the 1000 Bull Genomes variant catalogue resulted in the detection of a single homozygous protein-changing variant exclusively present in both sequenced genomes. This single-nucleotide deletion in exon 3 of IL17RA on bovine chromosome 5 was predicted to have a deleterious impact on the encoded protein due to a frameshift leading to a truncated gene product. Genotyping of the affected cattle family confirmed recessive inheritance. A loss-of-function mutation of the IL17RA transmembrane protein could be identified as most likely pathogenic variant for the psoriasis-like skin alterations observed in the two affected Holstein calves. In man, rare recessive diseases associated with IL17RA include immunodeficiency 51 and chronic mucocutaneous candidiasis. This supports the observed immunodeficiency of the presented cases. This study reports the first naturally occurring IL17RA-associated animal model.

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 > Department of Clinical Research and Veterinary Public Health (DCR-VPH)

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Häfliger, Irene Monika and Drögemüller, Cord

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 590 Animals (Zoology)
600 Technology > 610 Medicine & health
600 Technology > 630 Agriculture

ISSN:

1471-2156

Publisher:

BioMed Central

Language:

English

Submitter:

Cord Drögemüller

Date Deposited:

27 May 2020 11:19

Last Modified:

01 Sep 2020 20:16

Publisher DOI:

10.1186/s12863-020-00860-4

BORIS DOI:

10.7892/boris.144292

URI:

https://boris.unibe.ch/id/eprint/144292

Actions (login required)

Edit item Edit item
Provide Feedback