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Hepatic fibrinogen storage disease (HFSD) was diagnosed in a 5‐month‐old Wagyu calf with a history of recurrent respiratory disease. It was characterized by lethargy, dehydration, acidemia, and increased liver enzyme activities. Histologically, disseminated hepatocytes were swollen and showed a single, sharply demarcated, faintly eosinophilic cytoplasmic inclusion with a ground‐glass appearance, with the nucleus in an eccentric position. Cytoplasmic inclusions did not stain with the periodic acid‐Schiff (PAS) reaction. Using a rabbit polyclonal antibody against fibrinogen, the cytoplasmic vacuoles in the hepatocytes stained intensely. Electron microscopy disclosed hepatocytes with membrane‐bound cytoplasmic inclusions filled with fine granular material interspersed with a few coarse‐grained electron‐dense granules. A trio whole‐genome sequencing approach identified a deleterious homozygous missense variant in DGKG (p.Thr721Ile). The allele frequency in 209 genotyped Wagyu was 7.2%. This is a report of a DGKG‐related recessive inherited disorder in cattle and adds DGKG to the list of candidate genes for HFSD in other species. [ABSTRACT FROM AUTHOR]

Background: A recessive form of MOCOS‐associated xanthinuria type II is described in Tyrolean grey cattle. A similar case was identified in a 5‐month‐old Brown Swiss calf with hoof overgrowth, rough coat, urine sediment, and pneumonia. Hypothesis/Objectives: To characterize the disease phenotype, to evaluate its genetic etiology, and to determine the prevalence of the deleterious allele in the Brown Swiss population. Animals: An affected calf, its parents, and 65 441 Swiss dairy cattle. Methods: The affected animal was clinically examined and necropsied. Microarray genotyping was used to determine the genotypes and to assess the frequency of the MOCOS allele in a Brown Swiss control cohort. Results: Ultrasonography revealed hyperechoic renal pyramids with multifocal distal shadowing and echogenic sediment in the urinary bladder. Necropsy revealed suppurative bronchopneumonia and urolithiasis. Histology revealed numerous nephroliths with multifocal chronic lymphohistiocytic interstitial infiltrates, fibrosis, tubular degeneration, chronic multifocal glomerulonephritis with sclerosis, and bilateral hydronephrosis. Dysplastic changes were observed in the corium of the claw and the cornea. Genetic testing identified the homozygous presence of a known MOCOS frameshift variant in the case. Both parents were heterozygous and the prevalence of carriers in genotyped Brown Swiss cattle was 1.4% (342/24337). Conclusions and Clinical Importance: The findings were consistent with the diagnosis of a recessive renal syndrome similar to xanthinuria type II described in Tyrolean grey cattle. The prevalence of the deleterious MOCOS allele is low in the Brown Swiss breed. However, mating of carriers should be avoided to prevent further losses. [ABSTRACT FROM AUTHOR]

In this study, epilepsy with focal seizures progressing to generalized seizures was diagnosed in a 6‐month‐old Holstein heifer. The seizures were characterized by a brief pre‐ictal phase with depression and vocalization. During the ictal phase eyelid spasms, tongue contractions, nodding and abundant salivation were observed, rapidly followed by a convulsive phase with bilateral tonic, clonic or tonic–clonic activity and loss of consciousness. Finally, during the postictal phase the heifer was obtunded and disorientated, unable to perceive obstacles and hypermetric, and pressed its head against objects. In the inter‐seizure phase, the heifer was clinically normal. Neuropathology revealed axonal degeneration in the brainstem and diffuse astrocytic hypertrophic gliosis. Whole genome sequencing of the affected heifer identified a private heterozygous splice‐site variant in DYRK1B (NM_001081515.1: c.‐101‐1G>A), most likely resulting in haploinsufficiency owing to loss‐of‐function. This represents a report of a DYRK1B‐associated disease in cattle and adds DYRK1B to the candidate genes for epilepsy. [ABSTRACT FROM AUTHOR]

Hemifacial microsomia (HFM) was diagnosed in a 9‐day‐old Romagnola calf. The condition was characterized by microtia of the left ear, anotia of the right ear, asymmetry of the face, and deafness. Magnetic resonance imaging revealed agenesis of the right pinna and both tympanic bullae, asymmetry of the temporal bones and temporomandibular joints, and right pontine meningocele. Brainstem auditory evoked responses confirmed the impaired auditory capacity. At gross post mortem examination, there was agenesis and hypoplasia of the right and the left external ear, respectively. No histological abnormalities were detected in the inner ears. A trio whole‐genome sequencing approach was carried out and identified a private homozygous missense variant in LAMB1 affecting a conserved residue (p.Arg668Cys). Genotyping of 221 Romagnola bulls revealed a carrier prevalence <2%. This represents a report of a LAMB1‐related autosomal recessive inherited disorder in domestic animals and adds LAMB1 to the candidate genes for HFM. [ABSTRACT FROM AUTHOR]

Palatoschisis (also called cleft palate, CP) is an opening or cleft in the upper lip, the roof of the palate, or both, and is a common defect in both humans and domestic animals (Mossey & Modell, [4]; Mulvihill et al., [5]). Inherited forms of I MYH3 i -related human syndromes, including cleft palate, are known (OMIM 160720). The affected gene, I MYH3 i , encodes the myosin heavy chain 3 protein, which is known to be responsible for muscle contraction. [Extracted from the article]

A 6‐day‐old Belgian Blue‐Holstein calf was referred because of a syndrome resembling epidermolysis bullosa simplex (EBS). The clinical phenotype included irregular and differently sized erosions and ulcerations spread over the body, in particular on the limbs and over bone prominences, as well as in the nasal planum and oral mucosa. Blisters were easily induced by rubbing the skin. The skin lesions displayed a clear dermal‐epidermal separation at the level of the basal cell layer. Post mortem examination revealed erosions in the pharynx, proximal esophagus, and rumen. Whole‐genome sequencing revealed a heterozygous disruptive in‐frame deletion variant in KRT5 (c.534_536delCAA). Genotyping of both parents confirmed the variant as de novo mutation. Clinicopathological and genetic findings were consistent with the diagnosis of KRT5‐related EBS providing the second example of a spontaneous mutation causing epidermolysis bullosa in cattle. [ABSTRACT FROM AUTHOR]

This identified two heterozygous private protein-changing variants present exclusively in the genome of the affected calf and absent in both parental genomes as well as in 5365 controls (Table S1). Sanger sequencing confirmed the presence of the heterozygous I NUMB i variant in the affected calf and its sire, which clearly carried the mutant allele at a low level in comparison with the wild type allele, representing a germinal mosaic (Figure S1). A germline de novo variant in NUMB associated with a double-outlet right ventricle in Chianina cattle. [Extracted from the article]

These variants were absent from a total of 5365 controls and a single variant affects I SGSH i , a putative candidate gene for the observed congenital anomaly. Congenital amastia is a rare developmental disorder characterised by the complete absence of the mammary gland and teats (Huppert & Zidenberg, 2008). [Extracted from the article]

Osteochondrodysplasias comprise a broad spectrum of hereditary developmental disorders of bone and cartilage, but can also have significant effects on tendons, ligaments, and muscles (Warman et al., 2011). This heterozygous variant at chr1:152807533C>CA represents a 1-bp insertion in exon 2 of the I ANKRD28 i gene that directly affect the translation initiation (start) codon (XM 024989836.1: c.2dupT; Figure S1). COMMENTS We propose the heterozygous c.2dupT variant as a candidate causative variant for the observed congenital disorder and I ANKRD28 i as a novel candidate gene for dwarfism phenotypes. [Extracted from the article]

The deletion spanning 19 coding exons of the I COL2A1 i gene was subsequently evaluated by performing a multiplex PCR across both breakpoints, revealing an additional PCR product only in the affected calf (Fig. The I COL2A1 i gene has a probability of loss-of-function intolerance score of 1, meaning that it clearly falls into the class of loss-of-function haploinsufficient genes.11 Consequently, the observed phenotype could be explained by the non-expression of the mutant allele. This report presents another large structural variant affecting the I COL2A1 i gene causing a novel form of bovine achondrogenesis type II that occurred in combination with the perosomus elumbis (PE) phenotype (OMIA 000789-9913). [Extracted from the article]