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Article

KCNG1-Related Syndromic Form of Congenital Neuromuscular Channelopathy in a Crossbred Calf

1
Department of Veterinary Medical Sciences, University of Bologna, 40064 Ozzano Emilia, Italy
2
Institute of Genetics, Vetsuisse Faculty, University of Bern, 3012 Bern, Switzerland
3
Department of Comparative Biomedicine and Food Science, University of Padova, 35020 Legnaro, Italy
*
Author to whom correspondence should be addressed.
Academic Editor: Emilia Bagnicka
Genes 2021, 12(11), 1792; https://doi.org/10.3390/genes12111792
Received: 18 October 2021 / Revised: 29 October 2021 / Accepted: 10 November 2021 / Published: 12 November 2021
(This article belongs to the Section Animal Genetics and Genomics)
Inherited channelopathies are a clinically and heritably heterogeneous group of disorders that result from ion channel dysfunction. The aim of this study was to characterize the clinicopathologic features of a Belgian Blue x Holstein crossbred calf with paradoxical myotonia congenita, craniofacial dysmorphism, and myelodysplasia, and to identify the most likely genetic etiology. The calf displayed episodes of exercise-induced generalized myotonic muscle stiffness accompanied by increase in serum potassium. It also showed slight flattening of the splanchnocranium with deviation to the right side. On gross pathology, myelodysplasia (hydrosyringomielia and segmental hypoplasia) in the lumbosacral intumescence region was noticed. Histopathology of the muscle profile revealed loss of the main shape in 5.3% of muscle fibers. Whole-genome sequencing revealed a heterozygous missense variant in KCNG1 affecting an evolutionary conserved residue (p.Trp416Cys). The mutation was predicted to be deleterious and to alter the pore helix of the ion transport domain of the transmembrane protein. The identified variant was present only in the affected calf and not seen in more than 5200 other sequenced bovine genomes. We speculate that the mutation occurred either as a parental germline mutation or post-zygotically in the developing embryo. This study implicates an important role for KCNG1 as a member of the potassium voltage-gated channel group in neurodegeneration. Providing the first possible KCNG1-related disease model, we have, therefore, identified a new potential candidate for related conditions both in animals and in humans. This study illustrates the enormous potential of phenotypically well-studied spontaneous mutants in domestic animals to provide new insights into the function of individual genes. View Full-Text
Keywords: cattle; channelopathy; skeletal muscle; neuromuscular disorder; paradoxical myotonia congenita; potassium voltage-gated channel; precision medicine; hydrosyringomyelia; craniofacial dysmorphism cattle; channelopathy; skeletal muscle; neuromuscular disorder; paradoxical myotonia congenita; potassium voltage-gated channel; precision medicine; hydrosyringomyelia; craniofacial dysmorphism
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MDPI and ACS Style

Jacinto, J.G.P.; Häfliger, I.M.; Akyürek, E.E.; Sacchetto, R.; Benazzi, C.; Gentile, A.; Drögemüller, C. KCNG1-Related Syndromic Form of Congenital Neuromuscular Channelopathy in a Crossbred Calf. Genes 2021, 12, 1792. https://doi.org/10.3390/genes12111792

AMA Style

Jacinto JGP, Häfliger IM, Akyürek EE, Sacchetto R, Benazzi C, Gentile A, Drögemüller C. KCNG1-Related Syndromic Form of Congenital Neuromuscular Channelopathy in a Crossbred Calf. Genes. 2021; 12(11):1792. https://doi.org/10.3390/genes12111792

Chicago/Turabian Style

Jacinto, Joana G. P., Irene M. Häfliger, Eylem Emek Akyürek, Roberta Sacchetto, Cinzia Benazzi, Arcangelo Gentile, and Cord Drögemüller. 2021. "KCNG1-Related Syndromic Form of Congenital Neuromuscular Channelopathy in a Crossbred Calf" Genes 12, no. 11: 1792. https://doi.org/10.3390/genes12111792

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