A novel mutation of the CLCN1 gene in a cat with myotonia congenita: Diagnosis and treatment

Abstract

Case description: A 10-month-old castrated male domestic longhair cat was evaluated for increasing frequency of episodic limb rigidity.

Clinical findings: The cat presented for falling over and lying recumbent with its limbs in extension for several seconds when startled or excited. Upon examination, the cat had hypertrophied musculature, episodes of facial spasm, and a short-strided, stiff gait.

Diagnostics: Electromyography (EMG) identified spontaneous discharges that waxed and waned in amplitude and frequency, consistent with myotonic discharges. A high impact 8-base pair (bp) deletion across the end of exon 3 and intron 3 of the chloride voltage-gated channel 1 (CLCN1) gene was identified using whole genome sequencing.

Treatment and outcome: Phenytoin treatment was initiated at 3 mg/kg po q24 h and resulted in long-term improvement.

Clinical relevance: This novel mutation within the CLCN1 gene is a cause of myotonia congenita in cats and we report for the first time its successful treatment.

Keywords: chloride channel; electromyography; nondystrophic myotonia; phenytoin.

FIGURE 1

Alignment of the nucleotide sequence from the proband (affected cat) against the reference sequence (UCSC felCat9, top) verifies the presence of an 8 bp deletion at the location chrA2:15897085‐15897092 in chloride voltage‐gated channel 1 (CLNC1)

FIGURE 2

(A) The wild‐type nucleotide and codon sequence at the end of exon 3 and the beginning of intron 3 of feline chloride voltage‐gated channel 1 (CLNC1) is shown, with the corresponding reading frame highlighted in yellow. (B) The mutated nucleotide sequence is shown with the deleted nucleotides blacked out, and the adjusted reading frame is highlighted in yellow. The new codon sequence showing the creation of a stop codon is presented below

FIGURE 3

The predicted wild‐type and mutant protein structures of chloride voltage‐gated channel 1 (CLNC1), as modeled by I‐Tasser and visualized in Geneious Prime. The pink color represents alpha helices and yellow represents beta sheets