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.

中文翻译：

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荷斯坦牛家族中的一种IL17RA移码变体，具有牛皮癣样皮肤改变和免疫缺陷。

背景技术由于细菌，真菌或环境危险因素，牛的皮肤病变和皮肤病通常与感染相关。具有遗传病因的皮肤病已在牛中得到描述。在这些罕见疾病中，有与遗传的营养缺陷有关的原发性先天性皮肤病，例如牛遗传性锌缺乏症或锌缺乏症样综合征。这项研究介绍了三例在单个农场观察到的先天性皮肤病变的荷斯坦牛，它们类似于锌缺乏症综合征。在两个病例中进行了密切的临床和病理检查。家谱分析表明，对两个受影响的牛犊进行常染色体隐性遗传和全基因组测序。结果两只小牛生长迟缓，患有严重的溃疡性皮炎，伴有过度角化，糠疹，脱发和皮下脓肿形成。血液分析显示白细胞增多症与嗜中性白血球相对应，而矿物质，大量和微量营养素均在参考范围内。针对1000个Bull Genomes变异目录的变异调用和过滤导致检测到仅存在于两个测序基因组中的单个纯合蛋白质改变变异。预测牛染色体5上IL17RA外显子3中的这种单核苷酸缺失对编码蛋白具有有害影响，这是由于移码导致基因产物被截断。受影响的牛科的基因分型证实了隐性遗传。结论IL17RA跨膜蛋白功能丧失突变可被确定为在两只受影响的荷斯坦牛犊中观察到的牛皮癣样皮肤变化的最可能的致病变异。在人类中，与IL17RA相关的罕见隐性疾病包括免疫缺陷51和慢性粘膜皮肤念珠菌病。这支持了所观察到的病例的免疫缺陷。这项研究报告了第一个自然发生的与IL17RA相关的动物模型。