Pedigree analysis and exclusion of alpha-tocopherol transfer protein (TTPA) as a candidate gene for neuroaxonal dystrophy in the American Quarter Horse.

Summary

Neuroaxonal dystrophy/equine degenerative myeloencephalopathy (NAD/EDM) is a progressive neurodegenerative condition affecting young horses across multiple breeds, producing clinical signs resembling ataxia that can significantly impact performance and welfare. Because the human equivalent of this disease—familial vitamin E deficiency—is caused by mutations in the alpha-tocopherol transfer protein gene (TTPA), researchers conducted pedigree analysis and genetic sequencing in affected American Quarter Horses to determine whether TTPA variants might explain the equine condition and to clarify the inheritance pattern of NAD/EDM. Through careful examination of affected and carrier animals, the team excluded TTPA as a causative gene for NAD/EDM in this population, indicating that whilst vitamin E metabolism remains relevant to understanding the disease, a different genetic mechanism is responsible. This finding refocused investigation efforts towards other candidate genes and reinforced the importance of establishing accurate modes of inheritance before pursuing targeted genetic therapies. For practitioners managing young horses with progressive neurological signs, the result emphasises that TTPA gene testing would not be diagnostic for NAD/EDM, and that multimodal management—including appropriate vitamin E supplementation and nutritional support—remains essential until definitive genetic markers are identified.

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Key Findings

• •Pedigree analysis was conducted to establish the mode of inheritance for NAD/EDM in American Quarter Horses
• •TTPA gene was sequenced and evaluated as a candidate gene for NAD/EDM
• •Alpha-tocopherol transfer protein (TTPA) was excluded as a candidate gene for NAD/EDM in the American Quarter Horse

Conditions Studied