Detection of a genetic mutation for myotonia congenita among Miniature Schnauzers and identification of a common carrier ancestor

Bhalerao, Dilip P; Rajpurohit, Yashoda; Vite, Charles H.; Giger, Urs

doi:10.2460/ajvr.2002.63.1443

Cited by 24 publications

(23 citation statements)

References 27 publications

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“…Mutations in CLCN1 have been identified in Australian cattle dogs, Miniature Schnauzers, Jack Russell terrier, and cats . Mutations in SCN4A have yet to be identified in dogs.…”

Section: Myotoniamentioning

confidence: 99%

“…Myotonia congenita has been described in the Miniature Schnauzer and is inherited as an autosomal recessive trait sharing features of Becker‐type myotonia in people. The disease results from a mutation in the skeletal muscle voltage‐dependent chloride channel, CLC‐1 . This mutation causes a shift in the voltage dependence of activation and decreases the probability of the chloride channel opening at physiologic voltages …”

Section: Myotoniamentioning

confidence: 99%

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Classification of Involuntary Movements in Dogs: Myoclonus and Myotonia

Lowrie¹,

Garosi

2017

Veterinary Internal Medicne

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Myoclonus is a sudden brief, involuntary muscle jerk. Of all the movement disorders, myoclonus is the most difficult to encapsulate into any simple framework. On the one hand, a classification system is required that is clinically useful to aid in guiding diagnosis and treatment. On the other hand, there is need for a system that organizes current knowledge regarding biological mechanisms to guide scientific research. These 2 needs are distinct, making it challenging to develop a robust classification system suitable for all purposes. We attempt to classify myoclonus as “epileptic” and “nonepileptic” based on its association with epileptic seizures. Myotonia in people may be divided into 2 clinically and molecularly defined forms: (1) nondystrophic myotonias and (2) myotonic dystrophies. The former are a group of skeletal muscle channelopathies characterized by delayed skeletal muscle relaxation. Many distinct clinical phenotypes are recognized in people, the majority relating to mutations in skeletal muscle voltage‐gated chloride (CLCN1) and sodium channel (SCN4A) genes. In dogs, myotonia is associated with mutations in CLCN1. The myotonic dystrophies are considered a multisystem clinical syndrome in people encompassing 2 clinically and molecularly defined forms designated myotonic dystrophy types 1 and 2. No mutation has been linked to veterinary muscular dystrophies. We detail veterinary examples of myotonia and attempt classification according to guidelines used in humans. This more precise categorization of myoclonus and myotonia aims to promote the search for molecular markers contributing to the phenotypic spectrum of disease. Our work aimed to assist recognition for these 2 enigmatic conditions.

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“…Mutations in CLCN1 have been identified in Australian cattle dogs, Miniature Schnauzers, Jack Russell terrier, and cats . Mutations in SCN4A have yet to be identified in dogs.…”

Section: Myotoniamentioning

confidence: 99%

Section: Myotoniamentioning

confidence: 99%

Classification of Involuntary Movements in Dogs: Myoclonus and Myotonia

Lowrie¹,

Garosi

2017

Veterinary Internal Medicne

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“…Once all breeding dogs are screened and parentage is assured, there may thereafter no longer be a need for screening. Similarly, beneficial effects by genotype screening were seen with various other serious hereditary disease traits in specific canine breeds including copper toxicosis 23 , leukocyte adhesion deficiency 24 , and myotonia congenita 25 .…”

Section: Discussionmentioning

confidence: 96%

An exonic insertion in the NAGLU gene causing Mucopolysaccharidosis IIIB in Schipperke dogs

Raj

Ellinwood

Giger

2020

Sci Rep

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Mucopolysaccharidosis (MPS) IIIB (Sanfilippo syndrome B; OMIM 252920), is a lysosomal storage disease with progressive neurological signs caused by deficient activity of alpha-Nacetylglucosaminidase (NAGLU, EC 3.2.1.50). Herein we report the causative variant in the NAGLU gene in Schipperke dogs and a genotyping survey in the breed. All six exons and adjacent regions of the NAGLU gene were sequenced from six healthy appearing and three affected Schipperkes. DNA fragment length and TaqMan assays were used to genotype privately owned Schipperkes. A single variant was found in exon 6 of MPS IIIB affected Schipperkes: an insertion consisting of a 40-70 bp poly-A and an 11 bp duplication of the exonic region preceding the poly-A (XM_548088.6:c.2110_21 11ins[A(40_70);2100_2110]) is predicted to insert a stretch of 13 or more lysines followed by either an in-frame insertion of a repeat of the four amino acids preceding the lysines, or a frameshift. The clinically affected Schipperkes were homozygous for this insertion, and the sequenced healthy dogs were either heterozygous or homozygous for the wild-type allele. From 2003-2019, 3219 Schipperkes were genotyped. Of these, 1.5% were homozygous for this insertion and found to be clinically affected, and 23.6% were heterozygous for the insertion and were clinically healthy, the remaining 74.9% were homozygous for the wild-type and were also clinically healthy. The number of dogs homozygous and heterozygous for the insertion declined rapidly after the initial years of genotyping, documenting the benefit of a DNA screening program in a breed with a small gene pool. In conclusion, a causative NAGLU variant in Schipperke dogs with MPS IIIB was identified and was found at high frequency in the breed. Through genotyping and informed breeding practices, the prevalence of canine MPS IIIB has been drastically reduced in the Schipperke population worldwide.

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“…The diagnosis of myotonia congenita can be based on early onset, clinical signs, myotonic discharges in electromyography, histopathological and immunohistochemical changes of the muscle, and the absence of pathohistological features of other organs. In ChowChows and Miniature Schnauzers myotonia congenita has been described with difficulties in getting up, falling down due to excitement, 'bunny-hopping' gait, stridorous breathing, high-pitched bark, regurgitation, muscle hypertrophy, and percussion myotonia (Amann et al, 1985;Vite et al, 1998;Bhalareo et al, 2002). The symptoms progress with age.…”

Section: Discussionmentioning

confidence: 99%

“…Other organs are not involved. In Miniature Schnauzers the disease is caused by mutations in both alleles of genes encoding the skeletal muscle voltage-dependent chloride channel ClC-1 (Vite et al, 1998;Rhodes et al, 1999;Bhalareo et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Myotonic dystrophy in two European grey wolves ( Canis lupus )

Pákozdy

Leschnik

Nell

et al. 2007

Acta Veterinaria Hungarica

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Two related European Grey wolves (Canis lupus) with the history of muscle stiffness beginning at 2 weeks of age were examined in this study. Muscle tone and muscle mass were increased in both animals. Muscle stiffness was worsened by stress so that the animals fell into lateral recumbency. Blood chemistry revealed mildly increased serum creatine kinase activity. Abnormal potentials typical of myotonic discharges were recorded by electromyography. Cataract, first-degree atrioventricular (AV) block and inhomogeneous myocardial texture by ultrasound suggested extramuscular involvement. Myopathology demonstrated dystrophic signs in the muscle biopsy specimen. The presumptive diagnosis based on the in vivo findings was myotonic dystrophy. Immunochemistry of the striated muscles revealed focal absence of dystrophin 1 and beta-dystroglycan in both cases. Cardiac and ophthalmologic involvement suggested a disorder very similar to a human form of myotonic dystrophy. This is the first description of myotonic dystrophy in wolves.

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Detection of a genetic mutation for myotonia congenita among Miniature Schnauzers and identification of a common carrier ancestor

Abstract: A PCR-based enzyme digestion DNA test was developed. The mutant allele for this disease is frequent in Miniature Schnauzers that are related to a common carrier ancestor. Breeding dogs should be tested by this specific DNA test to help limit the spread of this deleterious mutation.

Cited by 24 publications

References 27 publications

Classification of Involuntary Movements in Dogs: Myoclonus and Myotonia

Classification of Involuntary Movements in Dogs: Myoclonus and Myotonia

An exonic insertion in the NAGLU gene causing Mucopolysaccharidosis IIIB in Schipperke dogs

Myotonic dystrophy in two European grey wolves ( Canis lupus )

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