Publication Database

EFNB3 frameshift variant in Weimaraner dogs with synchronous bunny-hopping gait (2024)

Art

Poster

Autoren

Schwarz, Cleo

Bartenschlager, Florian (WE 12)

Kershaw, Olivia (WE 12)

Braun, Judith

Epplen, Jörg T.

Jagannathan, Vidhya

Reinekin, Wencke

Baumgärtner, Wolfgang

Gruber, Achim (WE 12)

Leeb, Tosso

Kongress

12th International conference of canine and feline genetics and genomics

Helsinki, 09. – 12.06.2024

Quelle

12th International conference of canine and feline genetics and genomics : programme & abstracts

Helsinki, 2024 — S. 118

Sprache

Englisch

Verweise

URL (Volltext): https://www.helsinki.fi/assets/drupal/2024-06/ICCFGG%202024%20Programme%20%26%20Abstract%20Book.pdf

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
14163 Berlin
+49 30 838 62450
pathologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

We investigated three Weimaraner puppies from a litter of eleven that presented with hind limb weakness and a synchronous bunny-hopping gait at the age of 4 weeks. All three dogs were euthanized due to the unfavorable prognosis. The initial pathological examination was unremarkable. Combined linkage and autozygosity mapping delineated a 43.2 Mb critical interval. Whole genome sequencing data of the three cases were compared to 1491 control genomes and revealed a private homozygous frameshift variant in EFNB3 encoding ephrin-B3, a transmembrane ligand for Eph receptor tyrosine kinases which mediate various developmental processes, including axon guiding in the nervous system. During neurodevelopment, ephrin-B3 prevents contralateral corticospinal axons from recrossing the spinal cord midline, thus allowing for unilateral motor control. The identified variant, XM_038536724.1:c.643_644dupGG introduces a premature stop codon and is predicted to result in the truncation of 13% of the wild-type open reading frame, XP_038392652.1:p.(Ala216fs*79). Genotypes of 130 additional unaffected Weimaraner dogs were consistent with a monogenic autosomal-recessive mode of inheritance and identified additional heterozygous carrier animals. The existing functional knowledge of EFNB3 together with our findings suggest the identified variant as the potential causative variant for the observed phenotype. So far, comparable phenotypes have only been documented in genetically engineered mice. We provide the first report of an EFNB3-related neurodevelopmental disorder in dogs. It remains to be seen whether a similar EFNB3-related disorder involving loss of independent left-right movement coordination also occurs in human patients.