Identification of a recessive PCDH15 nonsense variant in purebred goats with vestibular dysfunction

Petzl, Eva ; Jacinto, Joana ; Climent Aroz, María (Universidad de Zaragoza) ; Suntz, Michael ; Karl, Michael ; Plobner, Lutz ; Matiasek, Kaspar ; Fischer, Andrea ; Hannemann, Regina ; Balasopoulou, Viktoria ; Zerbe, Holm ; Brühschwein, Andreas ; Drögemüller, Cord ; Letko, Anna

Resumen: Genetic diseases in goats are less well characterized than in other livestock species. This study reports a previously unrecognized congenital neurological disorder in Bunte Deutsche Edelziege goats and identifies its likely
genetic cause. Between 2019 and 2023, a dairy goat farm observed 21 kids with congenital vestibular disease. The affected kids displayed pronounced, sometimes exuberant, wide bilateral excursions of the head and neck, delayed standing, wide-based stance, and poor postural control, while remaining alert and physically strong. Motor coordination improved with age. One retained female displayed mild persistent deficits and suspected
hearing impairment in adulthood. Postmortem examinations were unremarkable, and infectious or nutritional causes were excluded. The repeated occurrence and pedigree structure suggested an inherited autosomal recessive disorder. Whole-genome sequencing of two affected kids, compared with large control cohorts, revealed a single rare nonsense variant in exon 5 of the PCDH15 gene encoding protocadherin-15. This variant truncates approximately 93% of the protein and is homologous to a pathogenic variant that causes Usher syndrome type 1F in humans. Sanger sequencing confirmed homozygosity in affected animals and heterozygosity in obligate carriers. The variant was absent from 90 unrelated goats of the same breed and over 1600 global controls. These findings indicate a naturally occurring Usher syndrome-like disorder in goats, representing the first such report, and highlight the value of genomic diagnostics for disease prevention and comparative research. The study provides a basis for the molecular diagnosis of similarly affected animals, as well as for genetic testing to prevent further cases.

Idioma: Inglés

DOI: 10.1016/j.vas.2026.100626

Año: 2026

Publicado en: Veterinary and Animal Science 32, [7 pp.] (2026), 100626
ISSN: 2451-943X

Tipo y forma: Article (Published version)

Área (Departamento): Área Anatom.Anatom.Patológ.Com (Dpto. Anatom.,Embri.Genét.Ani.)