Categories: Nervous system phene

Links to MONDO diseases: No links.

Mendelian trait/disorder: unknown

Considered a defect: yes

Species-specific name: Equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy

Species-specific symbol: eNAD/EDM

Species-specific description: In a detailed review, Finno and Johnson (2022) stated "it was apparent that eNAD [equine NeuroAxonal Dystrophy; OMIA:000715-9796 : Neuroaxonal dystrophy, generic in Equus caballus] was clinically indistinguishable from EDM [Equine Degenerative Myeloencephalopathy; this OMIA entry], and the current consensus is that the conditions have such striking clinical and pathologic similarities that eNAD could be considered a localized form of EDM or EDM a more diffuse form of eNAD."

Inheritance: Posbergh et al. (2018): "The ABD [autozygosity by difference] score difference pattern suggests an autosomal recessive pattern of inheritance [in the Caspian breed] . . . [but] . . . the recessive inheritance pattern seen here contrasts with other studies of EDM in other breeds".

Mapping: Using the novel Autozygosity-by-Difference (ADB) method, Posbergh et al. (2018) mapped this disorder in the Caspian breed to ECA3:71,381,589-73,566,775 (equCab2), which contains just one gene, namely ADGRL3, encoding adhesion G protein-coupled receptor L3. Leeb (2109) questioned this mapping result, partly on the basis that the controls were not breed-matched with the cases. From Posberg et al. (2018), it appears that the 90 controls comprised almost all of a panel of 96 horses made up of 48 Thoroughbreds and 3 each of 16 other breeds, including 3 Caspians. In responding, Posbergh et al. (2019) defended their mapping result, but admitted that "Using a variety of controls reduces the chances of this correction [the breed correction that is key to the use of controls in the ADB method] taking place".

Molecular basis: Posbergh et al. (2018) reported a positional candidate missense SNP in the ADGRL3 gene at ECA3:71770084; c.?A>G; p.Asn?Ser. Noting that the only two surviving homozygotes for this variant within this breed do not show any clinical signs, Posbergh et al. (2018) cautiously described the variant as "a genetic risk factor, working in conjunction with environmental factors, in the development of the EDM in the Caspian breed". Responding to doubts raised by Leeb (2019), Posbergh et al. (2019) concluded that "We do not assert that the investigated change [i.e. the above variant] is causative of equine degenerative myeloencephalopathy (EDM) disease." This conclusion was reinforced by Marquardt et al. (2019) who, having investigated the above variant and related variants in "31 postmortem-confirmed eNAD [Equine neuroaxonal dystrophy]/EDM cases and 43 clinically phenotyped controls from various breeds", concluded that "the four SNPs, including the missense variant in the ADGRL3 region, are not associated with risk for eNAD/EDM across multiple breeds of horses".

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

Clinical features: Marquardt et al. (2019): "Equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (eNAD/EDM) is a neurologic disease that has been reported in young horses from a wide range of breeds. Equine degenerative myeloencephalopathy (EDM) is a more histologically advanced form of equine neuroaxonal dystrophy (eNAD)."

Breed: Caspian (Horse) (VBO_0000930).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below