A KCNJ10 mutation previously identified in the Russell group of terriers also occurs in Smooth-Haired Fox Terriers with hereditary ataxia and in related breeds

Background

Hereditary ataxias with similar phenotypes were reported in the Smooth-Haired Fox Terrier, the Jack Russell Terrier and the Parson Russell Terrier. However, segregation analyses showed differing inheritance modes in these breeds. Recently, molecular genetic studies on the Russell group of terriers found independent mutations in KCNJ10 and CAPN1, each associated with a specific clinical subtype of inherited ataxia. The aim of this study was to clarify whether or not Smooth-Haired Fox Terriers with hereditary ataxia and dogs of other related breeds harbor either of the same mutations. A sub goal was to update the results of KCNJ10 genotyping in Russell group terriers.

Findings

Three Smooth-Haired Fox Terriers with hereditary ataxia and two Toy Fox Terriers with a similar phenotype were all homozygous for the KCNJ10 mutation. The same mutation was also found in a heterozygous state in clinically unaffected Tenterfield Terriers (n = 5) and, in agreement with previous studies, in Jack Russell Terriers, Parson Russell Terriers, and Russell Terriers.

Conclusions

A KCNJ10 mutation, previously associated with an autosomal recessive spinocerebellar ataxia in Jack Russell Terriers, Parson Russell Terriers, and Russell Terriers segregates in at least three more breeds descended from British hunting terriers. Ataxic members of two of these breeds, the Smooth-Haired Fox Terrier and the Toy Fox Terrier, were homozygous for the mutation, strengthening the likelihood that this genetic defect is indeed the causative mutation for the disease known as “hereditary ataxia” in Fox Terriers and “spinocerebellar ataxia with myokymia, seizures or both” in the Russell group of terriers.     

Mucopolysaccharidosis type VI in a Miniature Poodle-type dog caused by a deletion in the arylsulphatase B gene

Abstract

AIM: To investigate and characterise an inborn error of metabolism in a dog with skeletal and ocular abnormalities.

METHODS: A 2.5-year-old small male Miniature Poodle-like dog was presented with gross joint laxity and bilateral corneal opacities. Clinical examination was augmented by routine haematology, serum chemistry, radiographs, pathology, enzymology and molecular genetic studies. Euthanasia was requested when the dog was 3 years of age because of progressively decreasing quality of life.

RESULTS: Radiology revealed generalised epiphyseal dysplasia, malformed vertebral bodies, luxation/subluxation of appendicular and lumbosacral joints with hypoplasia of the odontoid process and hyoid apparatus. These clinical and radiographic findings, together with a positive urinary Berry spot test for mucopolysaccharides, and metachromatic granules in leucocytes, were indicative of a mucopolysaccharidosis (MPS), a lysosomal storage disease. Histological lesions included vacuolation of stromal cells of the cornea, fibroblasts, chondrocytes, macrophages and renal cells. The brain was essentially normal except for moderate secondary Wallerian-type degeneration in motor and sensory tracts of the hind brain. Dermatan sulphate-uria was present and enzymology revealed negligible activity of N-acetylgalactosamine-4-sulphatase, also known as arylsulphatase B, in cultured fibroblasts and liver tissue. A novel homozygous 22 base pair (bp) deletion in exon 1 of this enzyme's gene was identified (c.103_124del), which caused aframe-shift and subsequent premature stop codon. The “Wisdom pure breed-mixed breed” test reported the dog as a cross between a Miniature and Toy Poodle.

CONCLUSIONS: The clinicopathological features are similar to those of MPS type VI as previously described in dogs, cats and other species, and this clinical diagnosis was confirmed by enzymology and molecular genetic studies. This is an autosomal recessively inherited lysosomal storage disease.

CLINICAL RELEVANCE: The prevalence of MPS VI in Miniature or Toy Poodles in New Zealand and elsewhere is currently unknown. Due to the congenital nature of the disorder, malformed pups may be subject to euthanasia without investigation and the potential genetic problem in the breed may not be fully recognised. The establishment of a molecular genetic test now permits screening for this mutation as a basis to an informed breeding policy.     

改进的模拟退火算法在蛋白质结构预测中的应用

在传统的模拟退火算法基础上,对于产生新解边界值的处理给出一种新方法,并将它应用到二维Toy模型.对4条Fibonacci序列进行了结构预测,结果表明该算法可行有效.     

Congenital portosystemic shunts in toy and miniature poodles

Three male Poodles (two Toy, one Miniature) were presented to their veterinarians for evaluation of urolithiasis and varying degrees of hepatic encephalopathy. All three dogs were diagnosed as having intrahepatic shunts and referred for surgical correction. In each case, shunts arose from the right branch of the portal vein and were amenable to perivascular dissection caudal to where the vessel entered the hepatic parenchyma and to placement of perivascular cellophane bands to achieve shunt attenuation. During the same period, a female Miniature Poodle also presented for treatment of a congenital portosystemic shunt discovered during evaluation for generalised motor seizures. This animal had an extrahepatic portoazygous shunt that was completely ligated. Congenital portosystemic shunts have not previously been identified in Toy and Miniature Poodles at the University Veterinary Centre, Sydney and the anatomical types of shunt seen in this breed have not previously been reported in a consecutive series of cases. The three male dogs are noteworthy for a number of reasons: all had intrahepatic shunts, despite being small breed dogs; all three presented in a similar fashion, and all had shunts of an anatomical type amenable to placement of cellophane bands. One male dog died within 12 hours of surgery, the remaining three dogs survived and their liver function was normal at follow-up between 2 and 3 months after surgery. Use of cellophane bands for successful attenuation of intrahepatic shunts has not been previously reported.     

Topical allogeneic platelet-rich plasma treatment for a massive cutaneous lesion induced by disseminated intravascular coagulation in a toy breed dog

A 2-year-old intact female miniature Pinscher weighing 1.7 kg with a body condition score of 2/5 was presented for acute vomiting, lethargy for 2 days, and large petechial skin lesions on the hip region including the tail. Acute pancreatitis was diagnosed by clinical signs, strong positive cPLI test, laboratory test and ultrasound appearance. While the clinical signs associated with acute pancreatitis had improved in 3–5 days, lesion of petechial appeared on the left hip region 7 days after the presentation, with a fast progression into a necrotic tissue along the left side hip. Allogenic platelet rich plasma (PRP) with Weibrich and Kleis method was administered to promote skin healing and regeneration. Gradual and complete improvement in the dog’s wound lesions was noted approximately 1 month after applying allogeneic topical PRP. In this case report, allogeneic PRP was applied to a large regional cutaneous defect caused by coagulopathy induced by acute pancreatitis. Topical application of PRP in this case was unique in that allogeneic PRP was used instead of autologous PRP for the first time in cutaneous soft-tissue wound management in the veterinary medical field.     

GM2 Gangliosidosis Variant 0 (Sandhoff‐Like Disease) in a Family of Toy Poodles

Background: GM2 gangliosidosis variant 0 (human Sandhoff disease) is a lysosomal storage disorder caused by deficiencies of acid β‐hexosaminidase (Hex) A and Hex B because of an abnormality of the β‐subunit, a common component in these enzyme molecules, which is coded by the HEXB gene. Objective: To describe the clinical, pathological, biochemical, and magnetic resonance imaging (MRI) findings of Sandhoff‐like disease identified in a family of Toy Poodles. Animals: Three red‐haired Toy Poodles demonstrated clinical signs including motor disorders and tremor starting between 9 and 12 months of age. The animals finally died of neurological deterioration between 18 and 23 months of age. There were some lymphocytes with abnormal cytoplasmic vacuoles detected. Methods: Observational case study. Results: The common MRI finding was diffuse T2‐hyperintensity of the subcortical white matter in the cerebrum. Bilateral T2‐hyperintensity and T1‐hypointensity in the nucleus caudatus, and atrophic findings of the cerebrum and cerebellum, were observed in a dog in the late stage. Histopathologically, swollen neurons with pale to eosinophilic granular materials in the cytoplasm were observed throughout the central nervous system. Biochemically, GM2 ganglioside had accumulated in the brain, and Hex A and Hex B were deficient in the brain and liver. Pedigree analysis demonstrated that the 3 affected dogs were from the same family line. Conclusions and Clinical Importance: The Sandhoff‐like disease observed in this family of Toy Poodles is the 2nd occurrence of the canine form of this disease and the 1st report of its identification in a family of dogs.     

Dystrophin-deficient muscular dystrophy in a Toy Poodle with a single base pair insertion in exon 45 of the Duchenne muscular dystrophy gene

A 10-month-old, intact male Toy Poodle was referred for a postural abnormality. Blood biochemical tests revealed a marked increase in plasma creatine phosphokinase (CPK) concentration. The isoenzyme test showed that 99% of serum CPK consisted of CPK-MM. Histopathological evaluation of muscle biopsy samples confirmed scattered degeneration and necrosis of myofibers. Immunohistochemistry for dystrophin showed an absence of staining in muscle cells. Based on these findings, the dog was diagnosed with dystrophin-deficient muscular dystrophy. Whole genome sequencing using genomic DNA extracted from blood revealed a single base pair insertion in exon 45 of the Duchenne muscular dystrophy (DMD) gene. This is the first report on muscular dystrophy in Toy Poodles and identified a novel mutation in the DMD gene.     

Three hundred and three dogs with cataracts seen in Rio de Janeiro, Brazil

Objective  To describe the most common canine breeds affected with cataracts in Rio de Janeiro.
Animals  Three hundred and three dogs were included in this retrospective study. Animal ages ranged from 6 months to 14.8 years.
Material and methods  All records of dogs seen by the Ophthalmology Service of Policlínica Veterinária Botafogo between January 2005 and June 2008 were reviewed. Animals with cataracts were separated, and breed and age were evaluated.
Results  Most of the dogs presented with cataracts were Toy Poodles with a mean age of 8.2 years, followed by Cocker Spaniels and Bichon Frises. The percentage of Toy Poodles affected with cataracts was 13.8% while 33.3% of Bichon Frise was diagnosed with cataracts.
Conclusions  Toy Poodles are a popular breed in Rio de Janeiro. Without regulations on breeding, the prevalence of cataracts may increase rapidly. Furthermore, due to the relatively late onset of cataract formation in the Toy Poodle (mean 8.2 years of age), affected animals may have produced several litters of puppies. This study emphasizes the importance of screening for the presence of inherited ocular abnormalities such as cataracts prior to breeding.     

1例贵宾犬单侧隐睾病的诊断与治疗

隐睾是公犬常见的泌尿生殖系统畸形,会导致其生育能力下降甚至不育,是影响生殖健康的潜在风险。对1例贵宾犬隐睾病的诊断、手术治疗及疗效进行了介绍。     

成年贵宾犬蛋白质需要量的研究(简报)

采用单因子试验设计,将12只成年贵宾犬(♂,2岁)随机分为3组(每组4只),喂以不同蛋白质水平(1.15 NRC1、.25 NRC1、.35 NRC)的全价饲粮,利用氮平衡试验研究了成年贵宾犬对多种蛋白原料配合日粮中蛋白质的需要量.结果表明:食入氮与存留氮之间的回归关系为:y1=10.76+1.73x1(P=0.15),可消化氮与存留氮的回归关系为:y2=6.35+1.63x2(P=0.04).当x1=0时,y1=10.76,即成年贵宾犬每天总氮最低需要量为10.76g.只-1,蛋白质最低需要量为67.28 g.只-1.当x2=0时,y2=6.35,即成年贵宾犬每天最低可消化氮需要量为6.35 g.只-1,最低可消化蛋白质需要量为39.66 g.只-1.