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

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.

Immediate versus delayed implant placement after anterior single tooth extraction: the timing randomized controlled clinical trial.

AIM: To compare need for bone augmentation, surgical complications, periodontal, radiographic, aesthetic and patient reported outcomes in subjects receiving implant placement at the time of extraction (Immediate Implant) or 12 weeks thereafter. METHODS: Subjects requiring single tooth extraction in the anterior and premolar areas were recruited in seven private practices. Implant position and choice of platform were restoratively driven. Measurements were performed by calibrated and masked examiners. RESULTS: IMI was unfeasible in 7.5% of cases. One hundred and 24 subjects were randomized. One implant was lost in the IMI group. IMI required bone augmentation in 72% of cases compared with 43.9% for delayed (p = 0.01), while wound failure occurred in 26.1% and 5.3% of cases, respectively (p = 0.02). At 1 year, IMI had deeper probing depths (4.1 ± 1.2 mm versus 3.3 ± 1.1 mm, p < 0.01). A trend for greater radiographic bone loss was observed at IMI over the initial 3-year period (p-trend < 0.01). Inadequate pink aesthetic scores were obtained in 19% of delayed and in 42% of IMI implant cases (p = 0.03). No differences in patient reported outcomes were observed. CONCLUSIONS: Immediate implant placement should not be recommended when aesthetics are important, IMI should be limited to selected cases. Longer follow-up is needed to assess differences in complication rates.