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 clinicopath-ologic 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 devia-tion to the right side. On gross pathology, myelodysplasia (hydrosyringomielia and segmental hy-poplasia) 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 het-erozygous 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, there-fore, 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.

Kcng1‐related syndromic form of congenital neuromuscular channelopathy in a crossbred calf

Akyurek E. E.;Sacchetto R.;
2021

Abstract

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 clinicopath-ologic 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 devia-tion to the right side. On gross pathology, myelodysplasia (hydrosyringomielia and segmental hy-poplasia) 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 het-erozygous 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, there-fore, 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.
2021
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11577/3428585
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