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

Objective-To develop a molecular genetic test to detect the mutant skeletal muscle chloride channel (CIC-1) allele that causes myotonia congenita in Miniature Schnauzers and to analyze the relationship of affected and carrier dogs. Animals-372 Miniature Schnauzers from the United States, Canada, Australia, and Europe that were tested between March 2000 and October 2001. Procedure-The sequence surrounding the mutation in the CIC-1 allele was amplified by use of a unique pair of primers. Polymerase chain reaction (PCR) products were digested with the restriction enzyme Hpy CH4 III and separated on a 6% polyacrylamide gel. Pedigrees from all available carrier and affected dogs were analyzed, and a composite pedigree was established. Results-Enzyme digestion of PCR products of the normal CIC-1 allele resulted in 3 fragments of 175, 135, and 30 bp, whereas PCR products of the mutant allele resulted in fragments of only 175 and 165 bp. Of the 372 Miniature Schnauzers, 292 (78.5%) were normal, 76 (20.4%) were carriers, and 4 (1.1%) were affected (myotonic) dogs. Frequency of the mutant allele was 0.113. Pedigree analysis revealed that a popular sire, documented to be a carrier, was a common ancestor of all carriers and affected dogs. Conclusions and Clinical Relevance-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.