Independent DSG4 frameshift variants in cats with hair shaft dystrophy.

Investigations of hereditary phenotypes in spontaneous mutants may help to better understand the physiological functions of the altered genes. We investigated two unrelated domestic shorthair cats with bulbous swellings of the hair shafts. The clinical, histopathological, and ultrastructural features were similar to those in mice with lanceolate hair phenotype caused by loss-of-function variants in Dsg4 encoding desmoglein 4. We sequenced the genomes from both affected cats and compared the data of each affected cat to 61 control genomes. A search for private homozygous variants in the DSG4 candidate gene revealed independent frameshift variants in each case, c.76del or p.Ile26fsLeu*4 in case no. 1 and c.1777del or p.His593Thrfs*23 in case no. 2. DSG4 is a transmembrane glycoprotein located primarily in the extracellular part of desmosomes, a complex of adhesion molecules responsible for connecting the keratin intermediate filaments of neighbouring epithelial cells. Desmosomes are essential for normal hair shaft formation. Both identified DSG4 variants in the affected cats lead to premature stop codons and truncate major parts of the open-reading frame. We assume that this leads to a complete loss of DSG4 function, resulting in an incorrect formation of the desmosomes and causing the development of defective hair shafts. Together with the knowledge on the effects of DSG4 variants in other species, our data suggest that the identified DSG4 variants cause the hair shaft dystrophy. To the best of our knowledge, this study represents the first report of pathogenic DSG4 variants in domestic animals.

Multiple follicular abnormalities in a 1-year old cat consistent with basaloid follicular hamartomas.

BACKGROUND: In humans, basaloid follicular hamartomas are benign follicular tumours, that can be solitary or multiple, in which case they show autosomal dominant inheritance. HYPOTHESIS/OBJECTIVES: This study describes clinical and histopathological findings observed in a young cat, which could be consistent with basaloid follicular hamartomas. CASE DESCRIPTION: Multiple follicular abnormalities, consistent with cutaneous diffuse basaloid follicular hamartomas, were observed in skin samples from a one-year old neutered domestic short hair cat. Clinical signs were diffuse symmetrical alopecia with exaggerated skin markings (ventral abdomen, thorax and medial aspects of the limbs) and intense follicular-centred thickening (face and feet). Microscopic lesions were characterised by multiple proliferative follicular abnormalities in all samples. The epidermis showed a very irregular surface with the follicles filled with variably pigmented keratin. The epithelial walls of the follicles had multiple small hyperplastic basaloid cells foci. In the superficial dermis under the epidermis and around the follicles, fibroblastic spindle-shaped mesenchymal cells with a homogeneous moderate density were present in the collagenous connective tissue. The interfollicular epidermis was also abnormal with multiple small proliferating trichoblastic foci originating from the basal layer. RNAscope testing for feline papillomavirus was negative. CONCLUSIONS AND CLINICAL RELEVANCE: This case report provides the first evidence of clinical and histopathological findings of multiple follicular abnormalities, consistent with cutaneous diffuse basaloid follicular hamartomas in a cat.

De multiples anomalies folliculaires, compatibles avec des hamartomes folliculaires basaloïdes diffus cutanés, ont été observées dans des échantillons de peau d'un chat domestique à poils courts castré âgé d'un an. Les signes cliniques étaient une alopécie diffuse symétrique avec des marques cutanées exagérées (abdomen ventral, thorax et face médiale des membres) et un épaississement folliculaire intense (face et pieds).

Múltiplas anormalidades foliculares, consistentes com hamartomas cutâneos foliculares basaloides difusos, foram observadas em amostras de pele de um gato doméstico de pelo curto castrado de um ano de idade. Os sinais clínicos foram alopecia simétrica difusa com marcações cutâneas exuberantes (abdômen, tórax e aspecto medial dos membros) e espessamento folicular central intenso (face e patas).

Se observaron múltiples anomalías foliculares, consistentes con hamartomas foliculares basaloides difusos cutáneos, en muestras de piel de un gato doméstico de pelo corto castrado de 1 año. Los signos clínicos fueron alopecia simétrica difusa con marcas cutáneas exageradas (abdomen ventral, tórax y cara medial de las extremidades) e intenso engrosamiento de la piel centrado en los folículos (cara y pies).

Description and characterization of a hair coat disorder in schipperkes.

BACKGROUND: Schipperkes develop bilaterally symmetrical alopecia preceded by lightening of the hair coat not associated with systemic clinical signs. The alopecia is presumptively diagnosed as Alopecia X but has never been investigated. HYPOTHESIS/OBJECTIVES: The purpose of this study was to describe clinical features, histopathological and laboratory abnormalities associated with symmetrical, noninflammatory alopecia in schipperkes. ANIMALS: Three healthy and eight affected schipperkes. METHODS AND MATERIALS: Complete blood count (CBC), serum chemistry panel, urinalysis (UA), urine cortisol: creatinine ratio (UCCR), total thyroxine (T4 ), free thyroxine by equilibrium dialysis (fT4 ed), thyroid stimulating hormone (TSH) and pre- and post-stimulation cortisol with sex hormone analyses were performed for all dogs. A minimum of two skin biopsy sites were sampled for histopathological evaluation. RESULTS: The CBC, serum chemistry panel, UA, T4 , fT4 ed, TSH and post-ACTH cortisol concentrations were normal for all dogs. Androstenedione concentrations were increased for all dogs; two of three healthy and five of eight affected dogs had increased post-ACTH androstenedione concentrations. Estradiol concentrations were increased for all healthy and four of eight affected dogs, with post-ACTH estradiol concentrations increased for all healthy and five of eight affected dogs. Progesterone concentrations were increased for two of three healthy and four of eight affected dogs. Post-ACTH progesterone concentrations were increased for one of three healthy and four of eight affected dogs. For one of three healthy and two of eight affected dogs, 17-hydroxyprogesterone concentrations were increased; post-ACTH 17-hydroxyprogesterone concentrations were increased in three of eight affected dogs only. Histopathology results from affected dogs were consistent with hair cycle arrest. CONCLUSIONS AND CLINICAL IMPORTANCE: This disorder resembles Alopecia X clinically and histologically.

A de novo germline mutation of DLX3 in a Brown Swiss calf with tricho-dento-osseus-like syndrome.

OBJECTIVE: A novel congenital disorder affecting a calf was observed, and its phenotype and genetic mutation identified. ANIMAL: A six-month-old female Brown Swiss calf. METHODS: Diagnostic investigation and whole genome sequencing of a case parent trio was performed. RESULTS: The calf had a dull kinky coat with mild hypotrichosis, and teeth with brown staining and enamel defects. Histological examination of skin biopsies was compatible with a follicular dysplasia. Radiography and computed tomography revealed thickening of the skull bones and large pulp cavities with a marked thinning of enamel affecting all teeth. A de novo germline mutation affecting the distal-less homeobox gene (DLX3) was identified. The 10 bp frameshift mutation in exon 3 of the bovine DLX3 gene is predicted to replace the second C-terminal transactivation domain of the wild-type protein by a recoded peptide of 99 amino acids without any sequence similarity. CONCLUSION AND CLINICAL IMPORTANCE: A causative mutation for a sporadic phenotype resembling human tricho-dento-osseous syndrome was identified after detection of a de novo germline mutation in the DLX3 gene.

Advances in Microbiology, Infectious Diseases and Public Health: Fungal Occurrence in the Hair and Skin of Symptomatic Pets in Turin, Italy.

Companion animals, often asymptomatic reservoir of fungi, can be important sources of infection in humans, due to the close contact with their owners. The present study was aimed to assess the occurrence of dermatophytes and other fungi isolated from pet dermatological lesions in Turin, Italy. Dermatological specimens were examined for fungal elements by direct microscopy and cultured to detect dermatophytes, other filamentous fungi and yeasts: 247 pets (118 cats, 111 dogs and 18 dwarf rabbits) were positive for fungal detection in culture. Microsporum canis was the most frequent dermatophyte in cats and dogs, whereas Trichophyton mentagrophytes was the most common in rabbits. Among the other fungi, for all examined pets, dematiaceous fungi were the most isolated, followed by Mucorales, penicilli, yeasts and yeast-like fungi, and aspergilli. No gender predisposition was detected for dermatophyte growth; on the contrary, for the other fungi male cats were more susceptible than female. The highest fungal occurrence was recorded in <1-year-old cats for dermatophytes, and in <5-year-old cats and dogs for the other fungi. Autumn was the period associated with a relevant incidence of fungal infection. Finally, fungi were more frequent in non pure-breed cats and in pure-breed dogs. These data underline the importance to timely inform pet owners about the potential health risk of infection caused not only by dermatophytes but also by non-dermatophyte fungi, routinely considered to be contaminants or harmless colonizers, since their role as source of zoonotic infections is not to be excluded.

IMAGING DIAGNOSIS-NUCLEAR SCINTIGRAPHIC, RADIOLOGICAL, AND PATHOLOGIC CHARACTERISTICS OF METASTATIC PILOMATRICOMA IN A DOG.

A 6-year-old castrated Goldendoodle dog was presented for left-sided lameness of 3 weeks' duration. Focal, moderate to marked increased 99m Tc-methylene diphosphonate (99m Tc-MDP) uptake was detected in the right caudal lung lobe, caudal angle of the left scapula, and the distal aspect of the left femur with whole body bone phase scintigraphy. Radiographs identified a well-circumscribed, oval-shaped soft tissue opaque mass in the right caudal lung lobe; a suspect oval-shaped osteolytic lesion in the proximal third of the left scapula; and an osteolytic lesion in the distal aspect of the left femur. Metastatic pilomatricoma was confirmed histologically at all three sites.

A case of pili torti in a young adult domestic short-haired cat.

BACKGROUND: Pili torti is a congenital or acquired human disease characterized by flattening and twisting of the hair shaft by 180 degrees. A similar condition has been previously reported in a litter of kittens with generalized hair loss, associated with systemic signs and followed by death at a young age. ANIMAL: A 1-year-old castrated male domestic short-haired cat was presented for noninflammatory and nonpruritic symmetrical multifocal alopecia involving the head, pinnae, forelimbs, tail and chest. The cat was otherwise healthy. METHODS AND RESULTS: Microscopic examination of hair shafts revealed pili torti and a typical combination of anagen and telogen roots, occasionally spiral in shape, without evidence of mites or dermatophytes. Histopathological examination showed the same hair shaft abnormality, with normal epidermis, dermis, hair follicles and other adnexa. Scanning electron microscopy confirmed a hair shaft dysplasia characterized by pili torti, similar to that described in humans. CONCLUSIONS AND CLINICAL IMPORTANCE: To the best of the authors' knowledge, this is the first case report of pili torti in a healthy young adult cat.

Epitheliotropic T-cell lymphoma in a guinea pig.

A 4-year-old female guinea pig was presented with pruritic, erythematous, hypotrichotic and scaling skin lesions, mainly involving the abdomen and the hindlegs. Clinical abnormalities were limited to the skin, and the guinea pig was otherwise healthy. The dermatological diagnostic work-up excluded ectoparasites, dermatophytosis and an endocrinopathy as differential diagnoses for the pruritus and hair loss. An allergic dermatitis was under investigation when the general and skin condition deteriorated. A neoplastic skin disorder was suspected, and skin biopsies revealed changes consistent with a cutaneous epitheliotropic T-cell lymphoma. Pautrier's microabscesses and immunophenotyped CD3(+) CD79(-) lymphocytes were identified. Owing to the deteriorating condition of the animal and the unknown but most likely poor prognosis of this disease, the guinea pig was euthanized. To the authors' knowledge, this is the first case report of cutaneous epitheliotropic T-cell lymphoma in the guinea pig with characteristic histopathological and immunohistochemical features.

Histologic features of hair follicle neoplasms and cysts in dogs and cats: a diagnostic guide.

Hair follicle neoplasms occur in many different species, including humans. In domestic animals, they are most common in dogs. Most hair follicle tumors are benign, but malignant neoplasms can also occur. To diagnose hair follicle neoplasms, a thorough knowledge of follicular anatomy is important, given that follicular tumors are classified according to the differentiation pattern seen in the corresponding part of the normal hair follicle. This review focuses on the key diagnostic features of hair follicle tumors and follicular cysts in dogs and cats.

A mutation in NFkappaB interacting protein 1 causes cardiomyopathy and woolly haircoat syndrome of Poll Hereford cattle.

Cardiomyopathy and woolly haircoat syndrome (CWH) of Poll Hereford cattle is a lethal, autosomal recessive disorder. Cardiac and haircoat changes are congenital, neonatal ocular keratitis develops in some cases and death usually occurs within the first 12 weeks of life. We undertook a homozygosity mapping approach to identify the chromosomal location of the causative gene. Seven candidate genes were examined for homozygosity in affected animals: desmoplakin and junction plakoglobin (both previously implicated in human cardiocutaneous syndromes), desmocollin 2, desmoglein 2, plakophilin 2, nuclear factor kappa B (NFKB1) and NFkappaB interacting protein 1 (PPP1R13L, also known as NKIP1). Homozygosity in 13 affected animals was observed at the PPP1R13L locus, located on bovine chromosome 18. Subsequent sequence analysis revealed a 7-bp duplication (c.956_962dup7) in exon 6 of this 13-exon gene. This frameshift variant is predicted to result in the substitution of three amino acids and the introduction of a premature stop codon at position 325 of the protein product (p.Ser322GlnfsX4). PPP1R13L interacts with NFkappaB, a family of structurally related transcription factors that regulate genes controlling inflammation, immune responses and cell proliferation and survival. CWH represents a large-animal model for cardiocutaneous disorders caused by a mutation in the PPP1R13L gene. The identification of this bovine mutation also indicates that PPP1R13L and other genes affecting NFkappaB activity may be candidate genes in the study of human cardiovascular disease.

Desmoplastic tricholemmoma in a dog.

A 10-year-old mixed breed dog was presented with a 0.8 cm diameter mass below the left eye region. The mass was surgically removed and processed for histopathological examination. Microscopically, tumor cells proliferated in small lobules, nests and cords, and the tumor parenchyma was separated by desmoplastic stroma. Majority of the tumor cells were periodic acid-Schiff (PAS)-positive, and the desmoplastic stroma was densely collagenous and mucinous. Immunohistochemical results showed that the tumor cells were diffusely positive for cytokeratin 15, cytokeratin 19 and CD 34, while cytokeratin 8 reactivity was limited to the tumor cells proliferating in cords. Few tumor cells were positive for nestin. Based on the histopathological findings, the tumor was diagnosed as desmoplastic tricholemmoma.

Clinical and pathological features of hair coat abnormalities in curly coated retrievers from UK and Sweden.

OBJECTIVES: To gain information on hair loss amongst curly coated retrievers by questionnaire and to define the clinical and pathological features of hair coat abnormalities in affected dogs in the United Kingdom and Sweden. MATERIALS AND METHODS: Questionnaires were completed by members of the Curly Coated Retriever Clubs. Fourteen dogs (six in the United Kingdom, eight in Sweden) were clinically examined and skin/hair samples collected for microscopy and histopathology. Blood was collected for haematological, biochemical and endocrine assays. RESULTS: Of 90 dogs surveyed, 39 had current or previous episodes of symmetrical, non-pruritic alopecia and or frizzy coat changes, usually affecting caudal thighs, axillae, dorsum and neck before 18 months of age; 23 dogs had a waxing/waning course. Examined dogs generally matched the pattern described in questionnaires. Hair shaft anomalies comprised occasional distorted anagen bulbs (10 dogs) and transverse fractures (8 dogs). Vertical histopathological sections showed infundibular hyperkeratosis (28 of 30 sections) and low-grade pigment clumping (17 of 30). Subtle telogenisation of hair follicles was unequivocally confirmed by transverse histomorphometric analyses. CLINICAL SIGNIFICANCE: The follicular dysplasia of curly coated retriever reported here is similar to that of Irish water spaniels and Chesapeake Bay retrievers but distinct from that of Portuguese water dogs. The genetic basis requires further assessment.

Area of hock hair loss in dairy cows: risk factors and correlation with a categorical scale.

Data from 3691 dairy cows from 76 farms were used to investigate the risk factors associated with the area of hair loss over the lateral aspect of the hock and the correlation between the area of hair loss (as calculated using a hock map) and hock lesion scores determined using a pre-existing categorical scale. Six factors were associated with a greater area of hair loss, including cows with locomotion score 3, a cleanliness score (10/28 to 18/28), high daily milk yield (25.1-58.1 kg), poor body condition score (1-1.5), duration of winter housing (≥41 days) and some combinations of cubicle base and bedding materials. Compared with cows housed in cubicles with a concrete base and whole straw or rape straw bedding, cows housed in cubicles with concrete bases with sand or chopped straw bedding had smaller areas of hair loss and cows housed on a mattress base with whole straw or rape straw bedding had larger areas of hair loss. Area of hair loss, as measured on hock maps, was not significantly different between cows with score 1 (median 23.6 cm(2)) and score 2 (median 20.3 cm(2)) on the categorical scale for hock lesions. This suggests that the categorical scale was not reflecting the extent of hair loss and that hock maps are a good alternative for studying the dynamics of hock lesions over time.

Growth of populations of lice, Damalinia ovis, on sheep and their effects on production and processing performance of wool.

Merino sheep were artificially infested with lice, Damalinia ovis, and the quantity and processing performance of the wool they subsequently produced was compared with those of wool from uninfested sheep. The experiment was conducted in a winter rainfall region of Western Australia, and was repeated yearly for three years. Louse infestation depressed clean wool production by 0.3-0.8 kg per sheep but did not affect live weight. This represented loss of income to the farmer of about $A0.72 to $A1.92 for each louse-infested sheep. The wool from lice-infested sheep, when processed into tops, yielded 4.8 to 7.2% less top and noil, than wool from uninfested sheep and the tops had a lower mean fibre length. This was estimated to cost the processor $A20.79 to $A32.20 per 100 kg of wool processed which originated from lice-infested sheep. Louse populations built up during winter, spring and early summer to reach maximum sizes during mid or late summer when the sheep were shorn and removed from the experiment. In one group of infested sheep retained for the duration of the experiment, louse populations declined after shearing each summer. It appeared that shearing may be more important in limiting growth of louse populations than climatic factors.

Expression of cyclin kinase inhibitor p27(Kip1) in skin tumours of dogs.

Skin tumours (n=148) of epidermal or hair follicle origin were examined immunohistochemically to determine the expression of p27(Kip1)(p27), a cyclin-dependent kinase inhibitor (CDKI), and of Ki-67. In normal skin, a large number of basal cells of the epidermis and hair follicles were positive for Ki-67 and many suprabasal epithelial cells were positive for p27. Most of the hair matrix cells were positive for Ki-67 but negative for p27. Hair papillae were strongly positive for p27. Squamous cell carcinomas had a p27 positive index (PI) significantly lower than that of trichoepitheliomas (P<0.005), basal cell tumours (P<0.05) and intracutaneous cornifying epitheliomas (P<0.001). In contrast, Ki-67 PIs of squamous cell carcinomas and pilomatrixomas were significantly higher than those of trichoepitheliomas, basal cell tumours and intracutaneous cornifying epitheliomas (P<0.01 to P<0.001). No significant difference was observed between the Ki-67 PI values of squamous cell carcinomas and pilomatrixomas. The results suggested that p27 is capable of suppressing cell proliferation in the differentiation of normal canine skin. In spite of being a benign neoplasm, pilomatrixomas had a low p27 expression; this may be a reflection of the proliferative potential of the hair matrix. The expression of p27 may be a useful marker for the analysis of cell kinetics.

Cerebellar Purkinje's cell degeneration and coat color dilution in a family of Rhodesian Ridgeback dogs.

A syndrome of cerebellar Purkinje's cell degeneration and coat color dilution was diagnosed in a family of Rhodesian Ridgeback dogs. One male and 1 female from the same litter and 1 female from a different litter were evaluated for growth retardation, inability to ambulate, and progressive ataxia. On physical examination, lateral recumbency, severe ataxia, tremors, and diluted coat color were identified. Littermates with nondiluted coat color were neurologically normal. Results of routine laboratory tests, urine metabolic screenings, and karyotype analyses were normal. Histopathologic abnormalities at necropsy included cerebellar Purkinje's cell degeneration, reduced granular cell layer thickness, and uneven distribution of macromelanosomes within hair shafts. Pedigree analysis suggested an autosomal recessive mode of inheritance. This is the first description of a genetic syndrome affecting the central nervous system and associated with coat color dilution in dogs.

Cell proliferation kinetics in the hair root matrix of dogs with healthy skin and dogs with idiopathic seborrhea.

Cell proliferation kinetic values were established for the hair root matrix of primary anagen follicles of 14 Beagles and 4 Cocker Spaniels with healthy skin and 9 Cocker Spaniels with primary idiopathic seborrhea. Indices were established by intradermal pulse labeling with tritiated thymidine, followed by cutaneous biopsy and autoradiography. The hair root matrix cell labeling index was 23.4 +/- 3.5% for Beagles, 24.4 +/- 4.0% for healthy Cocker Spaniels, and 24.9 +/- 4.3% for seborrheic Cocker Spaniels. These values indicate a rapidly proliferating cell population. Differences among these cell kinetic data for the 3 groups of dogs were not statistically significant. Although significant cell kinetic differences have been reported for other epidermal structures (interfollicular epithelium, upper hair follicle external root sheath, sebaceous glands) in seborrheic Cocker Spaniels, proliferation of hair root matrix cells apparently remains unaffected.

Follicular cysts in sheep.

A flock of 188 sheep was surveyed for cutaneous lesions that were noticed 3 days after shearing. On the basis of histologic features of the cyst wall, ie, association with sebaceous glands and lack of follicular structures or rete pegs, the cysts were classified as follicular cysts.

Uveitis associated with poliosis and vitiligo in six dogs.

Idiopathic panuveitis with retinal detachment was associated with facial poliosis, vitiligo, and alopecia in 6 dogs; 4 were adult males. Dermatohistologic examination of affected facial sites from all dogs revealed a lichenoid dermatitis and unusual histiocytic cells. Intensive topical and systemic corticosteroid and topical mydriatic/cycloplegic therapy was successful in controlling uveitis in all dogs for variable periods. Three dogs, monitored for 12, 30, and 46 months, retained useful vision despite infrequent recurrence of uveitis. One dog was lost for subsequent examination. Two dogs were euthanatized and necropsied. Ocular histologic examination of these dogs revealed extensive granulomatous iridocyclitis and choroiditis, with retinal detachment and lenticular degeneration.

Escherichia coli and virus isolated from "sticky kits".

A total of 121 Escherichia coli strains isolated from 3-week-old mink kits were serotyped and examined for virulence factors. 56 strains were isolated from healthy kits while 65 were from "sticky kits". Among these, 34 different serotypes were detected. No difference in serotypes or the presence of virulence factors could be detected between healthy and diseased kits. By electron microscopy of faecal samples corona-, rota-, and calicivirus were demonstrated among healthy as well as diseased kits.