RESUMEN
BACKGROUND: Nine male and eight female calves born to a Normande artificial insemination bull named "Ly" were referred to the French National Observatory of Bovine Abnormalities for multiple fractures, shortened gestation, and stillbirth or perinatal mortality. RESULTS: Using Illumina BovineSNP50 array genotypes from affected calves and 84 half-sib controls, the associated locus was mapped to a 6.5-Mb interval on chromosome 19, assuming autosomal inheritance with germline mosaicism. Subsequent comparison of the whole-genome sequences of one case and 5116 control genomes, followed by genotyping in the affected pedigree, identified a de novo missense substitution within the NC1 domain of the COL1A1 gene (Chr19 g.36,473,965G > A; p.D1412N) as unique candidate variant. Interestingly, the affected residue was completely conserved among 243 vertebrate orthologs, and the same substitution in humans has been reported to cause type II osteogenesis imperfecta (OI), a connective tissue disorder that is characterized primarily by bone deformity and fragility. Moreover, three COL1A1 mutations have been described to cause the same syndrome in cattle. Necropsy, computed tomography, radiology, and histology confirmed the diagnosis of type II OI, further supporting the causality of this variant. In addition, a detailed analysis of gestation length and perinatal mortality in 1387 offspring of Ly and more than 160,000 progeny of 63 control bulls allowed us to statistically confirm in a large pedigree the association between type II OI and preterm delivery, which is probably due to premature rupture of fetal membranes and has been reported in several isolated cases of type II OI in humans and cattle. Finally, analysis of perinatal mortality rates and segregation distortion supported a low level of germ cell mosaicism in Ly, with an estimate of 4.5% to 7.7% of mutant sperm and thus 63 to 107 affected calves born. These numbers contrast with the 17 cases reported and raise concerns about the underreporting of congenital defects to heredo-surveillance platforms, even for textbook genetic syndromes. CONCLUSIONS: In conclusion, we describe a large animal model for a recurrent substitution in COL1A1 that is responsible for type II OI in humans. More generally, this study highlights the utility of such datasets and large half-sib families available in livestock species to characterize sporadic genetic defects.
Asunto(s)
Cadena alfa 1 del Colágeno Tipo I , Colágeno Tipo I , Mutación Missense , Osteogénesis Imperfecta , Animales , Bovinos/genética , Osteogénesis Imperfecta/genética , Osteogénesis Imperfecta/veterinaria , Colágeno Tipo I/genética , Masculino , Femenino , Enfermedades de los Bovinos/genética , Nacimiento Prematuro/genética , Nacimiento Prematuro/veterinaria , Linaje , EmbarazoRESUMEN
This review describes the clinical, radiographic and histologic characteristics of dentinogenesis imperfecta diagnosed in two unrelated young dogs without evidence of concurrent osteogenesis imperfecta. The dentition was noted to have generalized coronal discoloration ranging from grey-blue to golden brown. Clinical pulp exposure, coronal wear and fractures were observed as was radiographic evidence of endodontic disease, thin dentin walls or dystrophic obliteration of the pulp canal. The enamel was severely affected by attrition and abrasion despite histologically normal areas; loss was most likely due to poor adherence or support by the underlying abnormal dentin. Histologically, permanent and deciduous teeth examined showed thin, amorphous dentin without organized dentin tubules and odontoblasts had dysplastic cell morphology. Primary dentin disorders, including dentinogenesis imperfecta and dentin dysplasia, have been extensively studied and genetically characterized in humans but infrequently reported in dogs. Treatment in human patients is aimed at early recognition and multi-disciplinary intervention to restore and maintain normal occlusion, aesthetics, mastication and speech. Treatment in both humans and canine patients is discussed as is the documented genetic heritability of primary dentin disorders in humans.
Asunto(s)
Dentinogénesis Imperfecta , Enfermedades de los Perros , Osteogénesis Imperfecta , Humanos , Perros , Animales , Dentinogénesis Imperfecta/diagnóstico , Dentinogénesis Imperfecta/veterinaria , Dentinogénesis Imperfecta/genética , Estética Dental , Odontoblastos/patología , Osteogénesis Imperfecta/patología , Osteogénesis Imperfecta/veterinaria , Dentina , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/etiología , Enfermedades de los Perros/patologíaRESUMEN
We examined the clinical features and pathology, and identified the causative mutation, of osteogenesis imperfecta in a 2-mo-old kitten with growth retardation and abnormal gait. Blood and radiographic examinations were performed on presentation. Radiographs revealed decreased opacity of numerous bones. Fractures were observed in some long bones, including femur and tibia. Histologic examination of the tibia showed decreased osteoid and osteoblasts at the primary spongiosa extending from the growth plate. The periosteum was thickened, and cortical bone and osteoblasts were decreased. Consequently, osteogenesis imperfecta was diagnosed. Genomic DNA and total RNA were extracted from the skin and used for PCR. Whole-genome sequencing identified a 2-bp deletion (c.370_371delTG; p.C124fs), which resulted in a homozygous frameshift mutation on exon 3 of CREB3L1. This mutation introduced a premature stop codon, suggesting production of the truncated protein without a functional domain as a transcription factor for expression of COL1A1 mRNA. This error may have affected collagen fibril formation, leading to the development of osteogenesis imperfecta.
Asunto(s)
Enfermedades de los Gatos , Osteogénesis Imperfecta , Animales , Huesos , Enfermedades de los Gatos/diagnóstico por imagen , Enfermedades de los Gatos/genética , Gatos , Femenino , Mutación , Osteogénesis Imperfecta/diagnóstico , Osteogénesis Imperfecta/genética , Osteogénesis Imperfecta/veterinaria , Reacción en Cadena de la Polimerasa/veterinariaRESUMEN
Background: Neuromusculoskeletal anomalies generally in combination with severe clinical symptoms, comprise a heterogeneous group of fairly common and mostly fatal disorders in man and animals. Osteogenesis imperfecta (OI), also known as brittle bone disease, causes bone fragility and deformity. Prominent extra-skeletal accessory manifestations of OI comprise blue/gray sclerae, hearing impairment, lung abnormalities and hypercalciuria. Cases of OI in cattle have been reported. However, no causative mutations have been identified in cattle so far.Aim: To report a possible oligogenic origin identified in a calf from clinically healthy parents suffering from OI.Materials and Methods: A neonatal embryo transfer male Holstein calf developing multiple fractures with bone tissue showing marked osteopenia was used for whole genome re-sequencing as well as its parents. In addition, 2,612 randomly chosen healthy Holstein cattle were genotyped as well as controls.Results: Sixteen candidate genes with potential protein-altering variants were selected revealing non-synonymous variants only within IFITM5 and CRTAP genes. However, in-depth gene analysis did not result in the identification of a single causative mutation in the OI calf.Conclusion: The analysis of the OI case revealed a possible oligogenic origin of the disease attributable to additive effects of three candidate genes, i.e., ABCA13, QRFPR, and IFTIM5.Clinical relevance: Most OI cases in humans and domestic animals reported so far are caused by distinct dominant or recessive monogenic mutations, therefore a potential oligogenic additive genetic effect is a novel finding. Furthermore, the case presented here demonstrates that cross-species genetic analyses might not always be straightforward.
Asunto(s)
Enfermedades de los Bovinos/genética , Predisposición Genética a la Enfermedad/genética , Osteogénesis Imperfecta/veterinaria , Animales , Autopsia , Estudios de Casos y Controles , Bovinos , Enfermedades de los Bovinos/patología , Genotipo , Masculino , Herencia Multifactorial , Mutación/genética , Osteogénesis Imperfecta/genética , Osteogénesis Imperfecta/patologíaRESUMEN
A genetic disorder, osteogenesis imperfecta (OI) is broadly characterized by connective tissue abnormalities and bone fragility most commonly attributed to alterations in Type I collagen. Two Red Angus calves by the same sire presented with severe bone and dental fragility, blue sclera, and evidence of in utero fractures consistent with OI congenita. Comparative analyses with human cases suggested the OI in these calves most closely resembled that classified as OI Type II. Due to the phenotypic classification and shared paternity, a dominant, germ-line variant was hypothesized as causative although recessive genotypes were also considered due to a close relationship between the sire and dam of one calf. Whole-genome sequencing revealed the presence of a missense mutation in the alpha 1 chain of collagen Type I (COL1A1), for which both calves were heterozygous. The variant resulted in the substitution of a glycine residue with serine in the triple helical domain of the protein; in this region, glycine normally occupies every third position as is critical for correct formation of the Type I collagen molecule. Allele-specific amplification by droplet digital PCR further quantified the variant at a frequency of nearly 4.4% in the semen of the sire while it was absent in his blood, supporting the hypothesis of a de novo causative variant for which the germ line of the sire was mosaic. The identification of novel variants associated with unwanted phenotypes in livestock is critical as the high prolificacy of breeding stock has the potential to rapidly disseminate undesirable variation.
Asunto(s)
Enfermedades de los Bovinos/genética , Mutación de Línea Germinal , Osteogénesis Imperfecta/veterinaria , Alelos , Animales , Bovinos , Enfermedades de los Bovinos/metabolismo , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Femenino , Genes Dominantes , Masculino , Mutación Missense , Osteogénesis Imperfecta/genética , Osteogénesis Imperfecta/metabolismo , Linaje , FenotipoRESUMEN
Osteogenesis imperfecta (OI) is a genetic disease that occurs in humans and animals. Individuals with OI exhibit signs of extreme bone fragility and osteopenia with frequent fractures and perinatal lethality in severe cases. In this study, we report the clinical diagnosis of OI in a dog and the use of targeted next-generation sequencing to identify a candidate autosomal dominant mutation in the COL1A2 gene. A 5-month-old male Chow Chow was examined with a fractured left humerus and resolving, bilateral femoral fractures. Radiographs revealed generalized osteopenia and bilateral humeral, radial, and femoral fractures. Targeted next-generation sequencing of genes associated with OI in humans (COL1A1, COL1A2, LEPRE1, SERPINH1, and CRTAP) revealed a G>A heterozygous mutation in the splice donor site of exon 18 of the COL1A2 gene (c.936 + 1G>A). The splice donor mutation was not detected among 91 control dogs representing 21 breeds. A comparative analysis of exon 18 and the exon-intron junction further showed that the mutated splice donor site is conserved among vertebrates. Altogether, these findings reveal a candidate autosomal splice donor site mutation causing OI in an individual Chow Chow.
Asunto(s)
Colágeno Tipo I/genética , Enfermedades de los Perros/genética , Mutación , Osteogénesis Imperfecta/genética , Osteogénesis Imperfecta/veterinaria , Animales , Perros , Exones , Heterocigoto , Secuenciación de Nucleótidos de Alto Rendimiento , Masculino , Sitios de Empalme de ARNRESUMEN
One-year-old male Persian cat presented with multiple fractures and no known traumatic history. Marked decrease of bone radiopacity and thin cortices of all long bones were identified on radiography. Tentative diagnosis was osteogenesis imperfecta, a congenital disorder characterized by fragile bone. To determine bone mineral density (BMD), quantitative computed tomography (QCT) was performed. The QCT results revealed a mean trabecular BMD of vertebral bodies of 149.9 ± 86.5 mg/cm3. After bisphosphonate therapy, BMD of the same site increased significantly (218.5 ± 117.1 mg/cm3, p ï¼ 0.05). QCT was a useful diagnostic tool to diagnose osteopenia and quantify response to medical treatment.
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Enfermedades de los Gatos/diagnóstico por imagen , Osteogénesis Imperfecta/veterinaria , Animales , Densidad Ósea , Conservadores de la Densidad Ósea/uso terapéutico , Enfermedades de los Gatos/patología , Gatos , Difosfonatos/uso terapéutico , Masculino , Osteogénesis Imperfecta/diagnóstico por imagen , Osteogénesis Imperfecta/tratamiento farmacológico , Osteogénesis Imperfecta/patología , Radiografía/veterinaria , Tomografía Computarizada por Rayos X/veterinaria , Resultado del TratamientoRESUMEN
Osteogenesis imperfecta (OI) is a heritable connective tissue disease characterized by bone fragility and increased risk of fractures. Up to now, mutations in at least 18 genes have been associated with dominant and recessive forms of OI that affect the production or post-translational processing of procollagen or alter bone homeostasis. Among those, SERPINH1 encoding heat shock protein 47 (HSP47), a chaperone exclusive for collagen folding in the ER, was identified to cause a severe form of OI in dachshunds (L326P) as well as in humans (one single case with a L78P mutation). To elucidate the disease mechanism underlying OI in the dog model, we applied a range of biochemical assays to mutant and control skin fibroblasts as well as on bone samples. These experiments revealed that type I collagen synthesized by mutant cells had decreased electrophoretic mobility. Procollagen was retained intracellularly with concomitant dilation of ER cisternae and activation of the ER stress response markers GRP78 and phospho-eIF2α, thus suggesting a defect in procollagen processing. In line with the migration shift detected on SDS-PAGE of cell culture collagen, extracts of bone collagen from the OI dog showed a similar mobility shift, and on tandem mass spectrometry, the chains were post-translationally overmodified. The bone collagen had a higher content of pyridinoline than control dog bone. We conclude that the SERPINH1 mutation in this naturally occurring model of OI impairs how HSP47 acts as a chaperone in the ER. This results in abnormal post-translational modification and cross-linking of the bone collagen.
Asunto(s)
Colágeno Tipo I/metabolismo , Proteínas del Choque Térmico HSP47/genética , Osteogénesis Imperfecta/genética , Osteogénesis Imperfecta/veterinaria , Mutación Puntual , Animales , Huesos/química , Huesos/metabolismo , Huesos/patología , Células Cultivadas , Colágeno Tipo I/análisis , Modelos Animales de Enfermedad , Perros , Chaperón BiP del Retículo Endoplásmico , Estrés del Retículo Endoplásmico , Fibroblastos/metabolismo , Fibroblastos/patología , Proteínas del Choque Térmico HSP47/análisis , Proteínas del Choque Térmico HSP47/metabolismo , Osteogénesis Imperfecta/metabolismo , Osteogénesis Imperfecta/patología , Procesamiento Proteico-Postraduccional , Estabilidad ProteicaRESUMEN
O objetivo do estudo foi avaliar o efeito do enxerto ósseo corticoesponjoso na osteogênese em falha cortical ulnar de galinhas domésticas. Foram utilizadas 18 galinhas, com aproximadamente 70 semanas de idade e peso corpóreo médio de 2,5kg. Criou-se uma falha óssea na porção diafisária média da ulna em ambas as asas, sendo a direita utilizada como grupo-controle (grupo I) e a esquerda como grupo-tratado (grupo II). As aves foram subdivididas aleatoriamente em quatro subgrupos de acordo com o período de observação (14, 35, 60 e 90 dias). No grupo II, dois fragmentos ósseos da carena do esterno foram retirados, seccionados e implantados na falha óssea. Ao término do período de observação de cada subgrupo, as aves foram abatidas com tiopental sódico para realização dos exames histopatológico e radiográfico post-mortem, com classificação dos resultados em escala semiquantitativa (escore). O grupo II demonstrou osteogênese mais evidente aos 35 e 90 dias de pós-cirúrgico (P<0,05). Ao comparar os grupos I e II, sem levar-se em consideração o tempo de observação, foi possível observar que houve diferença estatística significativa (P<0,05). Conclui-se que o enxerto ósseo corticoesponjoso demonstra potencial osteogênico satisfatório na espécie estudada, entretanto retarda o tempo de remodelação óssea quando aplicado sobre falhas estáveis pequenas.
The aim of this survey was to evaluate the effect of cortico-cancellous bone grafting in osteogenesis in cortical ulnar failure in domestic chickens. Eighteen chickens weighing 2.5kg with approximately 70 weeks of age were used. A bone defect in the middle portion of the ulna shaft was created in both wings; the right wing in the control group (Group I) and the left in the treated group (Group II). The birds were randomly divided into four subgroups according to the observation period (14, 35, 60 and 90 days). In group II, two bone fragments of the keel of the sternum were removed, sectioned and implanted in the bone defects. At the end of the observation period for each subgroup, the birds were euthanaized with sodium thiopental to perform the histopathological and radiographic postmortem, with ranking of results in a semi-quantitative scale (score). Group II showed a more evident osteogenisis at 35 and 90 days after surgery (P<0.05). In comparing both groups, without time observation, there was statistical difference (P<0.05). In conclusion, the cortico-cancellous bone graft demonstrated satisfactory osteogenic potential in the specie studied, however, it delays the bone remodeling time when applied in stable small failures.
Asunto(s)
Animales , Femenino , Fracturas Óseas/patología , Fracturas Óseas/veterinaria , Osteogénesis Imperfecta/diagnóstico , Osteogénesis Imperfecta/veterinaria , Trasplante Óseo/veterinaria , Pollos/anomalíasRESUMEN
Osteogenesis imperfecta (OI) is a genetic disorder causing defects in the development of collagen type I. Clinical signs of affected dachshunds include multiple fractures of bones, joint hyperlaxity and dentinogenesis imperfecta. Recently, a recessive mutation in the SERPINH1 gene was detected in dachshunds and enabled the development of a DNA test to identify dachshunds carrying the mutation. The purpose of the present study was to analyse the dachshund breeding population for the frequency of the SERPINH1 mutation among the nine different breed varieties in dachshunds, birth years and countries of origin. We genotyped the OI-associated SERPINH1 mutation in 1352 dachshunds from 12 different European countries including all nine varieties. Genotyping was done using a restriction fragment length polymorphism validated by DNA sequence analysis. The overall frequency of OI carriers was 12.9 per cent. Across all different size varieties, the SERPINH1 mutation was over-represented in wire-haired dachshunds with 17.3 per cent OI carriers. Among the different countries, the proportion of OI carriers was highest in Germany with 20.4 per cent. The test is useful for dachshund breeders to prevent the occurrence of OI-affected dogs and as a diagnostic tool for veterinarians.
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ADN/análisis , Enfermedades de los Perros/genética , Proteínas del Choque Térmico HSP47/genética , Mutación , Osteogénesis Imperfecta/veterinaria , Animales , Enfermedades de los Perros/diagnóstico , Perros , Femenino , Genes Recesivos , Predisposición Genética a la Enfermedad , Pruebas Genéticas/veterinaria , Heterocigoto , Masculino , Osteogénesis Imperfecta/diagnóstico , Osteogénesis Imperfecta/genética , Linaje , Polimorfismo de Longitud del Fragmento de RestricciónRESUMEN
Osteogenesis imperfecta (OI) is a hereditary disease occurring in humans and dogs. It is characterized by extremely fragile bones and teeth. Most human and some canine OI cases are caused by mutations in the COL1A1 and COL1A2 genes encoding the subunits of collagen I. Recently, mutations in the CRTAP and LEPRE1 genes were found to cause some rare forms of human OI. Many OI cases exist where the causative mutation has not yet been found. We investigated Dachshunds with an autosomal recessive form of OI. Genotyping only five affected dogs on the 50 k canine SNP chip allowed us to localize the causative mutation to a 5.82 Mb interval on chromosome 21 by homozygosity mapping. Haplotype analysis of five additional carriers narrowed the interval further down to 4.74 Mb. The SERPINH1 gene is located within this interval and encodes an essential chaperone involved in the correct folding of the collagen triple helix. Therefore, we considered SERPINH1 a positional and functional candidate gene and performed mutation analysis in affected and control Dachshunds. A missense mutation (c.977C>T, p.L326P) located in an evolutionary conserved domain was perfectly associated with the OI phenotype. We thus have identified a candidate causative mutation for OI in Dachshunds and identified a fifth OI gene.
Asunto(s)
Enfermedades de los Perros/genética , Proteínas del Choque Térmico HSP47/genética , Osteogénesis Imperfecta/veterinaria , Animales , Perros , Humanos , Mutación Missense , Osteogénesis Imperfecta/genéticaAsunto(s)
Acrodermatitis/veterinaria , Modelos Animales de Enfermedad , Osteogénesis Imperfecta/veterinaria , Enfermedades de las Ovejas/genética , Zinc/deficiencia , Acrodermatitis/genética , Acrodermatitis/patología , Animales , Humanos , Osteogénesis Imperfecta/genética , Osteogénesis Imperfecta/patología , Ovinos , Enfermedades de las Ovejas/patologíaRESUMEN
A 4.5-month-old, male domestic shorthair was presented with bilateral femoral fractures after falling from a low height. Radiographs revealed reduced radio-opacity and thin cortices of all long bones. A presumptive diagnosis of osteodystrophy, secondary to osteogenesis imperfecta, was made on postmortem examination.
Asunto(s)
Enfermedades de los Gatos/diagnóstico , Osteogénesis Imperfecta/veterinaria , Animales , Enfermedades de los Gatos/diagnóstico por imagen , Gatos , Resultado Fatal , Fracturas del Fémur/etiología , Fracturas del Fémur/veterinaria , Masculino , Osteogénesis Imperfecta/complicaciones , Osteogénesis Imperfecta/diagnóstico , Osteogénesis Imperfecta/diagnóstico por imagen , RadiografíaRESUMEN
A clinical, morphologic, ultrastructural, and genetic study was performed on five rough-coated dachshund semisiblings with osteogenesis imperfecta (OI). Clinical signs consisted of pain, spontaneous bone and teeth fractures, joint hyperlaxity, and reduced bone density on radiography. Primary teeth were extremely thin-walled and brittle. The hallmark of the disease was a severe osteopenia characterized by impairment of lamellar bone formation in the long bones, skull, and vertebral column. No deformity or dwarfism was present. The columns of chondrocytes and primary trabeculae in the epiphyses and metaphyses were histologically normal. An abrupt failure of secondary spongiosa and lamellar bone formation was evident in the medullary and cortical zones in all animals. The few existing trabeculae consisted of woven bone. There was no increase in the number and size of osteoclasts or lacunae. In the teeth, the dentine layers were thin and lacked a tubular pattern. Ultrastructurally, osteoid apposition on bone surfaces was reduced, and small numbers of large cytoplasmic vacuoles were present in a few osteoblasts. Molecular analyses of the collagen type I-encoding genes COL1A1 and COL1A2 revealed several nucleotide differences compared with the published canine sequences but were not significant for OI. Therefore, OI in these Dachshund litters was characterized by a severe, generalized osteopenia and dentinopenia. This pattern of reduced bone formation is suggestive of defective production of collagen type I.
Asunto(s)
Enfermedades de los Perros/patología , Osteogénesis Imperfecta/veterinaria , Animales , Huesos/diagnóstico por imagen , Huesos/patología , Huesos/ultraestructura , Colágeno Tipo I/química , Colágeno Tipo I/genética , Enfermedades de los Perros/diagnóstico por imagen , Enfermedades de los Perros/genética , Perros , Femenino , Histocitoquímica/veterinaria , Masculino , Microscopía Electrónica/veterinaria , Osteogénesis Imperfecta/diagnóstico por imagen , Osteogénesis Imperfecta/genética , Osteogénesis Imperfecta/patología , Mutación Puntual , ARN/química , ARN/genética , Radiografía , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/veterinaria , Análisis de Secuencia de ADN/veterinaria , Diente/patologíaRESUMEN
When a young dog is evaluated for multiple fractures with minimal to no accompanying trauma, the primary differential diagnoses are metabolic disease, physical abuse, and osteogenesis imperfecta (OI). Of these, secondary hyperparathyroidism is most common, but if serum concentrations of ionized calcium, phosphorus, vitamin D, and parathormone are within reference ranges, OI must be considered. Osteogenesis imperfecta is a heritable disease characterized by brittle bones. Results of studies using cultured skin fibroblasts indicate that most cases of OI in human beings are caused by a mutation in a type-I collagen gene. Osteogenesis imperfecta was recently identified in 3 dogs. Radiographic findings included multiple fractures in various stages of healing and generalized osteopenia. Cultured fibroblasts from skin biopsy specimens were used to diagnose OI. Structural abnormalities were found in type-I collagen from each dog. This cell culture assay can be used to evaluate dogs with brittle bones.
Asunto(s)
Enfermedades de los Perros/diagnóstico , Osteogénesis Imperfecta/veterinaria , Animales , Enfermedades Óseas Metabólicas/diagnóstico , Enfermedades Óseas Metabólicas/diagnóstico por imagen , Enfermedades Óseas Metabólicas/veterinaria , Células Cultivadas , Colágeno/análisis , Colágeno/genética , Colágeno/metabolismo , Diagnóstico Diferencial , Enfermedades de los Perros/patología , Enfermedades de los Perros/fisiopatología , Perros , Electroforesis en Gel de Poliacrilamida/métodos , Electroforesis en Gel de Poliacrilamida/veterinaria , Femenino , Fémur/diagnóstico por imagen , Fémur/patología , Fibroblastos/química , Fibroblastos/metabolismo , Fibroblastos/patología , Masculino , Mutación , Osteogénesis Imperfecta/diagnóstico , Osteogénesis Imperfecta/fisiopatología , Radiografía , Piel/química , Piel/metabolismo , Piel/patología , Tibia/diagnóstico por imagen , Tibia/patologíaRESUMEN
Eight calves with osteogenesis imperfecta were born in a Danish Holstein-Friesian herd during a two-year period. In total 92 calves were born (84 normal), and all were sired by a clinically normal Holstein-Friesian bull. The defect was probably due to a de novo dominant mutation present as a gonadal mosaicism in the bull. Affected calves were characterised by multiple fractures, congenital bone deformations, general joint laxity, dentinogenesis imperfecta, and light blue sclerae. The skin seemed normal. Electron microscopical studies revealed slightly decreased average diameter of cutaneous collagen fibrils, while the diameter of collagen fibrils in tendons and ligaments was severely reduced. Abnormalities of collagen type I from skin and compact bone were not detected by biochemical analyses.
Asunto(s)
Enfermedades de los Bovinos/genética , Osteogénesis Imperfecta/veterinaria , Animales , Cruzamiento , Bovinos , Enfermedades de los Bovinos/patología , Femenino , Masculino , Mosaicismo , Mutación , Osteogénesis Imperfecta/genética , Osteogénesis Imperfecta/patologíaRESUMEN
A 12-year-old kitten was found to have bone fragility. Previously described causes of bone fragility in domestic cats were excluded on the basis of serum biochemical profile and radiographic histologic examinations. The findings in this kitten correlated most closely with osteogenesis imperfecta, a syndrome documented in human beings and cattle.