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

BMC Genetics

卷:21

Mark Holsteg¹  Marlene Sickinger²  Gesine Lühken³  Cord Drögemüller⁴  Irene M. Häfliger⁴  Leif M. Raeder⁵  Manfred Henrich⁵  Siegfried Marquardt⁶ 

[1] Bovine Health Service, Chamber of Agriculture of North Rhine-Westphalia;

[2] Clinic for Obstetrics, Gynecology and Andrology of Large and Small Animals with Ambulatory Service, Faculty of Veterinary Medicine, Justus-Liebig University Giessen;

[3] Institute of Animal Breeding and Genetics, Faculty of Agricultural Sciences, Nutritional Sciences and Environmental Management, Justus-Liebig University Giessen;

[4] Institute of Genetics, Vetsuisse Faculty, University of Bern;

[5] Institute of Veterinary Pathology, Faculty of Veterinary Medicine, Justus-Liebig-University Giessen;

[6] Veterinary Sharing Practice, Dr. Siegfried Marquardt and Peter Walter;

关键词: Cattle;    Genetic disorder;    Monogenic;    Mendelian;    Skin disorder;    Precision medicine;   

DOI  :  10.1186/s12863-020-00860-4

来源: DOAJ

【 摘 要 】

Abstract Background 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. Results 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. Conclusions 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.

【 授权许可】

Unknown