TY - JOUR
T1 - Congenital myasthenic syndrome in Golden Retrievers is associated with a novel COLQ mutation
AU - Tsai, Kate L.
AU - Vernau, Karen M.
AU - Winger, Kathryn
AU - Zwueste, Danielle M.
AU - Sturges, Beverly K.
AU - Knipe, Marguerite
AU - Williams, D. Colette
AU - Anderson, Kendall J.
AU - Evans, Jacquelyn M.
AU - Guo, Ling T.
AU - Clark, Leigh Anne
AU - Shelton, G. Diane
PY - 2020/1/1
Y1 - 2020/1/1
N2 - Background: Congenital myasthenic syndromes (CMSs) are a group of inherited disorders of neuromuscular transmission that may be presynaptic, synaptic, or postsynaptic. Causative mutations have been identified in 4 breeds including the Labrador Retriever, Jack Russell Terrier, Heideterrier, and Danish Pointing Dog. Hypothesis/Objective: Clinical and genetic characterization of a neuromuscular disorder in Golden Retriever (GR) puppies. Animals: Four GR puppies from California were evaluated for generalized muscle weakness beginning at weaning. Biological specimens were collected from the affected puppies, and familial information was obtained. Blood or buccal swabs were obtained from 63 unaffected GRs. Methods: Complete physical, neurological, electrodiagnostic, and histological evaluations and biochemical quantification of muscle acetylcholine receptors were performed. Polymerase chain reaction was used to amplify the 17 exons of COLQ, and sequences were obtained by Sanger sequencing. Variant frequency was assessed in unrelated GRs and a public database. Results: Clinical, neurological, and electrodiagnostic evaluations confirmed a disorder of neuromuscular transmission in a GR family. Sequencing of all exons and splice sites of a primary candidate gene, COLQ, identified a point mutation that predicts an amino acid substitution (G294R). The primary COLQ transcript was absent from affected muscle samples. All affected puppies were homozygous for the mutation, which was not detected outside this GR family or in other breeds. Conclusions and Clinical Importance: We confirmed the diagnosis of a CMS in GR puppies and identified a novel COLQ mutation. The COLQ gene encodes the collagenous tail of acetylcholinesterase, the enzyme responsible for termination of skeletal muscle contraction by clearing acetylcholine at the neuromuscular junction. Clinicians and breeders should be aware of this CMS in GR puppies with an early onset of weakness.
AB - Background: Congenital myasthenic syndromes (CMSs) are a group of inherited disorders of neuromuscular transmission that may be presynaptic, synaptic, or postsynaptic. Causative mutations have been identified in 4 breeds including the Labrador Retriever, Jack Russell Terrier, Heideterrier, and Danish Pointing Dog. Hypothesis/Objective: Clinical and genetic characterization of a neuromuscular disorder in Golden Retriever (GR) puppies. Animals: Four GR puppies from California were evaluated for generalized muscle weakness beginning at weaning. Biological specimens were collected from the affected puppies, and familial information was obtained. Blood or buccal swabs were obtained from 63 unaffected GRs. Methods: Complete physical, neurological, electrodiagnostic, and histological evaluations and biochemical quantification of muscle acetylcholine receptors were performed. Polymerase chain reaction was used to amplify the 17 exons of COLQ, and sequences were obtained by Sanger sequencing. Variant frequency was assessed in unrelated GRs and a public database. Results: Clinical, neurological, and electrodiagnostic evaluations confirmed a disorder of neuromuscular transmission in a GR family. Sequencing of all exons and splice sites of a primary candidate gene, COLQ, identified a point mutation that predicts an amino acid substitution (G294R). The primary COLQ transcript was absent from affected muscle samples. All affected puppies were homozygous for the mutation, which was not detected outside this GR family or in other breeds. Conclusions and Clinical Importance: We confirmed the diagnosis of a CMS in GR puppies and identified a novel COLQ mutation. The COLQ gene encodes the collagenous tail of acetylcholinesterase, the enzyme responsible for termination of skeletal muscle contraction by clearing acetylcholine at the neuromuscular junction. Clinicians and breeders should be aware of this CMS in GR puppies with an early onset of weakness.
KW - canine
KW - myasthenia gravis
KW - myopathy
KW - neuromuscular junction
UR - http://www.scopus.com/inward/record.url?scp=85075762482&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85075762482&partnerID=8YFLogxK
U2 - 10.1111/jvim.15667
DO - 10.1111/jvim.15667
M3 - Article
C2 - 31769119
AN - SCOPUS:85075762482
VL - 34
SP - 258
EP - 265
JO - Journal of Veterinary Internal Medicine
JF - Journal of Veterinary Internal Medicine
SN - 0891-6640
IS - 1
ER -