CJM – Cardiomyopathy and juvenile mortality in Belgian Shepherds

Cardiomyopathy with juvenile mortality (CJM) is an inherited disease characterized by early death of puppies at birth or at a maximum age of six to eight weeks. The puppies initially develop normally, but then they show unspecific clinical signs like vomiting, uncoordinated movements (trembling, stumbling) and respiratory problems (dyspnea). The puppies die several days after onset of the first clinical signs, usually due to heart failure.

This mutation is caused by mutation c. 1054G>A in YARS2 gene that encodes mitochondrial tyrosyl-tRNA synthetase 2. Eukaryotic organisms have two tyrosyl-tRNA synthetases – cytoplasmic (YARS1) and mitochondrial (YARS2).  These two types of synthetases have evolutionarily conserved sequence motifs (we can find them in animals, fungi, and even in plants) which points to the importance of conservation of correct sequence for the function of an organism. The mutation c. 1054G>A affects the function of YARS2 gene and hampers the correct recognition and binding of the mitochondrial tRNA. The loss of YARS2 function can also be observed in human patients who have similar symptoms as Belgian Shepherds and suffer from myopathy, lactic acidosis, anaemia and results in early death.

The mutation that causes the CJM is inherited autosomal recessively. The disease develops only in individuals that inherited the mutated gene from both parents. These individuals are designated as P/P (positive/positive). The carriers of the mutated gene referred to as N/P (negative/positive) have only one mutated gene from one parent and show no clinical symptoms. However, they pass on this disease to their offspring. Genetic testing can detect the presence of the mutated allele and prevent further spreading of this disease.

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Reference:

Gurtner, C., Hug, P., Kleiter, M., Köhler, K., Dietschi, E., Jagannathan, V., & Leeb, T. (2020). YARS2 Missense Variant in Belgian Shepherd Dogs with Cardiomyopathy and Juvenile Mortality. Genes, 11(3), 313.