Categories: Haematopoietic system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 231200 (trait) , 173515 (gene)

Links to relevant human diseases in MONDO:

• MONDO:0009276: Bernard-Soulier syndrome

Mendelian trait/disorder: yes

Mode of inheritance: Probably autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2019

Cross-species summary: also called platelet glycoprotein 1b deficiency; von Willebrand Factor receptor deficiency or giant platelet disorder

Molecular basis: Gentilini et al. (2019): "Whole genome sequencing of one affected dog and visual inspection of the [comparative] candidate genes identified a deletion in the glycoprotein IX platelet (GP9) gene. The GP9 gene encodes a subunit of a platelet surface membrane glycoprotein complex; this functions as a receptor for von Willebrand factor, which initiates the maintenance of hemostasis after injury. Variants in human GP9 are associated with Bernard-Soulier syndrome, type C. The deletion spanned 2460 bp, and included a significant part of the single coding exon of the canine GP9 gene on dog chromosome 20. The variant results in a frameshift and premature stop codon which is predicted to truncate almost two-thirds of the encoded protein. PCR-based genotyping confirmed recessive inheritance. The homozygous variant genotype seen in affected dogs did not occur in 98 control Cocker Spaniels."

Clinical features: Gentilini et al. (2019): "The affected dogs showed a platelet adhesion defect characterized by macrothrombocytopenia with variable platelet counts resembling human Bernard-Soulier syndrome (BSS). Furthermore, the lack of functional GPIb-IX-V was demonstrated by immunocytochemistry."

Prevalence: Gentilini et al. (2019): "the prevalence of the variant allele [in a sample of Cocker Spaniels from Switzerland and Italy] was 4.6% with a distribution of genotypes frequencies of 91.8% of homozygous wild-type, 7.1% of heterozygous and 1% of homozygous variant".

Breed: Cocker Spaniel (Dog) (VBO_0200372).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: