Open AccessCongenital myasthenic syndrome in Golden Retrievers is associated with a novel COLQ mutation
Author(s) -
Tsai Kate L.,
Vernau Karen M.,
Winger Kathryn,
Zwueste Danielle M.,
Sturges Beverly K.,
Knipe Marguerite,
Williams D. Colette,
Anderson Kendall J.,
Evans Jacquelyn M.,
Guo Ling T.,
Clark Leigh Anne,
Shelton G. Diane
Publication year - 2019
Publication title -
journal of veterinary internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.356
H-Index - 103
eISSN - 1939-1676
pISSN - 0891-6640
DOI - 10.1111/jvim.15667
Subject(s) - neuromuscular transmission , medicine , congenital myasthenic syndrome , sanger sequencing , acetylcholinesterase , neuromuscular junction , exon , mutation , genetics , muscle weakness , acetylcholine receptor , gene , biology , neuroscience , receptor , enzyme , biochemistry
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.