A Nonsense Variant in the ACADVL Gene in German Hunting Terriers with Exercise Induced Metabolic Myopathy

G3 : Genes - Genomes - Genetics
Vincent LeporiMarion Kornberg

Abstract

Several enzymes are involved in fatty acid oxidation, which is a key process in mitochondrial energy production. Inherited defects affecting any step of fatty acid oxidation can result in clinical disease. We present here an extended family of German Hunting Terriers with 10 dogs affected by clinical signs of exercise induced weakness, muscle pain, and suspected rhabdomyolysis. The combination of clinical signs, muscle histopathology and acylcarnitine analysis with an elevated tetradecenoylcarnitine (C14:1) peak suggested a possible diagnosis of acyl-CoA dehydrogenase very long chain deficiency (ACADVLD). Whole genome sequence analysis of one affected dog and 191 controls revealed a nonsense variant in the ACADVL gene encoding acyl-CoA dehydrogenase very long chain, c.1728C>A or p.(Tyr576*). The variant showed perfect association with the phenotype in the 10 affected and more than 500 control dogs of various breeds. Pathogenic variants in the ACADVL gene have been reported in humans with similar myopathic phenotypes. We therefore considered the detected variant to be the most likely candidate causative variant for the observed exercise induced myopathy. To our knowledge, this is the first description of this disease in dogs, wh...Continue Reading

References

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Citations

Sep 6, 2019·Animal Genetics·V JagannathanUNKNOWN Dog Biomedical Variant Database Consortium (DBVDC)
Aug 28, 2019·Journal of Neuromuscular Diseases·Inès BarthélémyLaurent Tiret

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Datasets Mentioned

BETA
PRJEB16012
SAMEA104125120

Methods Mentioned

BETA
transmission electron microscopy
PCR
genotyping
biopsies

Software Mentioned

Broad GATK HaplotypeCaller
- Aligner
SnpEff
Picard
VariantFilter GATK
Sequencher
NCSS
samtools
Burrows
Genome Analysis Tool Kit ( GATK

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