Hereditary myotonia in American Bulldog associated with a novel frameshift mutation in the CLCN1 gene

Rodrigues, Daiane de Jesus; Damasceno, Adilson Donizeti; Araújo, Cynthia Gobbi Alves; Torelli, Sandra Regina; Fonseca, Luine Gabriela Hilário; Delfiol, Diego José Zanzarini; Oliveira-Filho, José Paes de; Araújo-Junior, João Pessoa; Borges, Alexandre Secorun

doi:10.1016/j.nmd.2020.10.007

Cited by 10 publications

(18 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, in humans, higher concentrations of CK are described in people with myotonic dystrophy and a mild increase was also reported in a case report of a Chow Chow with congenital myotonia 21‐23 . Myotonia, delayed muscle relaxation after voluntary contraction or percussion, occurs in humans, goats, horses, mice, and dogs 24‐41 . ACTH and proopiomelanocortin mutations occur in human dystrophic myotonia 42 .…”

Section: Discussionmentioning

confidence: 85%

“…21 , 22 , 23 Myotonia, delayed muscle relaxation after voluntary contraction or percussion, occurs in humans, goats, horses, mice, and dogs. 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ACTH and proopiomelanocortin mutations occur in human dystrophic myotonia. 42 In dogs, myotonic signs occur in association with various muscle diseases, as a congenital condition, and in association with HC.…”

Section: Discussionmentioning

confidence: 99%

“… 42 In dogs, myotonic signs occur in association with various muscle diseases, as a congenital condition, and in association with HC. 2 , 3 , 4 , 5 , 6 , 7 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 Fewer than 20 dogs with HC and concurrent myotonia or SMS are reported. 2 , 3 , 4 , 5 , 6 , 7 …”

Section: Discussionmentioning

confidence: 99%

“…42 In dogs, myotonic signs occur in association with various muscle diseases, as a congenital condition, and in association with HC. [2][3][4][5][6][7][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] Fewer than 20 dogs with HC and concurrent myotonia or SMS are reported. [2][3][4][5][6][7] In the present study, the case summaries submitted by 14 colleagues from 10 institutions located in widely separated geographic areas yielded only 37 dogs with concomitant HC and SMS, underscoring the uncommon nature of this combination of conditions.…”

Section: Discussionmentioning

confidence: 99%

“…ACTH and proopiomelanocortin mutations occur in human dystrophic myotonia 42 . In dogs, myotonic signs occur in association with various muscle diseases, as a congenital condition, and in association with HC 2‐7,24‐41 . Fewer than 20 dogs with HC and concurrent myotonia or SMS are reported 2‐7 …”

Section: Discussionmentioning

confidence: 99%

See 4 more Smart Citations

Clinical features of muscle stiffness in 37 dogs with concurrent naturally occurring hypercortisolism

Golinelli

Fracassi

Bianchi

et al. 2023

Veterinary Internal Medicne

View full text Add to dashboard Cite

Background Severe muscle stiffness (SMS) in dogs with hypercortisolism (HC) is uncommon. Objectives To evaluate signalment, presentation, treatments, and long‐term outcomes of dogs with concurrent HC and SMS. Animals Thirty‐seven dogs. Methods Medical records of dogs with HC and concurrent SMS were recruited from 10 institutions. Clinical information, test results, therapeutic responses, and survival times were reviewed. Results All 37 dogs with HC and SMS had pituitary‐dependent hypercortisolism (PDH); 36/37 weighed <20 kg. Signs and test results were typical of PDH aside from SMS, initially diagnosed in all 4 limbs in 9, pelvic limbs of 22, and thoracic limbs of 6 dogs. Hypercortisolism and SMS were diagnosed together in 3 dogs; HC 1‐36 months before SMS in 23; SMS 1‐12 months before HC in 11. Mitotane or trilostane, given to control HC in 36/37 dogs, improved or resolved HC signs in 28; SMS did not resolve, remaining static or worsening in 31/36 dogs, mildly improving in 5/19 dogs given additional therapies. Progression of SMS included additional limbs in 10 dogs and the masticatory muscles of 2. The median survival time from diagnosis of SMS was 965 days (range, 8‐1188). Conclusions and Clinical Importance Concurrent SMS and HC is uncommon, possibly affecting only dogs with PDH. Development of SMS might occur before or after diagnosis of HC. Apart from SMS, the clinical picture and survival time of these dogs seem indistinguishable from those of dogs with HC in general. However, while muscle weakness usually resolves with HC treatment SMS does not.

show abstract

Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Clinical features of muscle stiffness in 37 dogs with concurrent naturally occurring hypercortisolism

Golinelli

Fracassi

Bianchi

et al. 2023

Veterinary Internal Medicne

View full text Add to dashboard Cite

show abstract

A loss-of-function variant in canine GLRA1 associates with a neurological disorder resembling human hyperekplexia

Heinonen

Flegel

Müller³

et al. 2023

Hum. Genet.

View full text Add to dashboard Cite

Hereditary hyperekplexia is a rare neuronal disorder characterized by an exaggerated startle response to sudden tactile or acoustic stimuli. In this study, we present a Miniature Australian Shepherd family showing clinical signs, which have genetic and phenotypic similarities with human hereditary hyperekplexia: episodes of muscle stiffness that could occasionally be triggered by acoustic stimuli. Whole genome sequence data analysis of two affected dogs revealed a 36-bp deletion spanning the exon–intron boundary in the glycine receptor alpha 1 (GLRA1) gene. Further validation in pedigree samples and an additional cohort of 127 Miniature Australian Shepherds, 45 Miniature American Shepherds and 74 Australian Shepherds demonstrated complete segregation of the variant with the disease, according to an autosomal recessive inheritance pattern. The protein encoded by GLRA1 is a subunit of the glycine receptor, which mediates postsynaptic inhibition in the brain stem and spinal cord. The canine GLRA1 deletion is located in the signal peptide and is predicted to cause exon skipping and subsequent premature stop codon resulting in a significant defect in glycine signaling. Variants in GLRA1 are known to cause hereditary hyperekplexia in humans; however, this is the first study to associate a variant in canine GLRA1 with the disorder, establishing a spontaneous large animal disease model for the human condition.

show abstract

Hereditary myotonia in cats associated with a new homozygous missense variant p.Ala331Pro in the muscle chloride channel ClC‐1

Corrêa,

Basso,

Cerri

et al. 2023

Veterinary Internal Medicne

Self Cite

View full text Add to dashboard Cite

Three‐related cats were evaluated for a history of short‐strided gait and temporary recumbency after startle. Neurological examination, electromyography (EMG), muscle biopsies, and a chloride voltage‐gated channel 1 (CLCN1) molecular study were performed. Clinically, all 3 cats presented myotonia with warm‐up phenomenon and myotonic discharges during EMG examination. Muscle biopsies showed normal muscle architecture and variation in the diameter of myofiber size with the presence of numerous hypertrophic fibers. The molecular study revealed a missense variant (c.991G>C, p.Ala331Pro) in exon 9 of the CLCN1 gene, responsible for the first chloride channel extracellular loop. This mutation was screened in 104 control phenotypically normal unrelated cats, and all were wildtype. The alanine at this position is conserved in ClC‐1 (chloride channel protein 1) in different species, and 2 mutations at this amino acid position are associated with human myotonia. This is the third CLCN1 mutation described in the literature associated with hereditary myotonia in cats and the first in domestic animals located in an extracellular muscle ClC‐1 loop.

show abstract

Hereditary myotonia in American Bulldog associated with a novel frameshift mutation in the CLCN1 gene

Cited by 10 publications

References 32 publications

Clinical features of muscle stiffness in 37 dogs with concurrent naturally occurring hypercortisolism

Clinical features of muscle stiffness in 37 dogs with concurrent naturally occurring hypercortisolism

A loss-of-function variant in canine GLRA1 associates with a neurological disorder resembling human hyperekplexia

Hereditary myotonia in cats associated with a new homozygous missense variant p.Ala331Pro in the muscle chloride channel ClC‐1

Contact Info

Product

Resources

About