Inherited nerve disease in Leonberger dogs linked to X chromosome

Abstract

BACKGROUND: Although reporting the same clinical phenotype, inherited polyneuropathy in Leonberger dogs (ILPN) has been attributed to various modes of inheritance. HYPOTHESIS: The ILPN is one disease with a major risk factor on chromosome X. ANIMALS: Dogs affected by ILPN (n = 104). METHODS: Pedigree analyses were performed by means of a case-control approach. Data were retrieved either from medical records of cases diagnosed by the first author (n = 13), from breeders (n = 18) or from different registries publishing data on affected dogs (n = 73). A comparison was made between the X-chromosome ancestry of fathers of affected male dogs and the ancestry of the X-chromosomes of mothers of affected dogs of either sex. A systematic random sample, obtained from an international database of registered Leonberger dogs, served as a reference population regarding ancestry. RESULTS: Having one particular female, born 1943, in the X-chromosomal lineage is a major risk factor for developing ILPN. Sex distribution among affected dogs is in favor of a risk factor on the X-chromosome and contradicts a monogenic autosomal or mitochondrial inheritance. CONCLUSIONS AND CLINICAL IMPORTANCE: The ILPN is considered most likely to be one disease, and the inheritance of ILPN is best explained by an underlying X-linked mode of transmission for the phenotype. However, age at onset and severity of signs might be determined by contributing loci. This has consequences in molecular genetic studies and for breeding strategies aimed at eliminating this disease.