Gp9, also known as glycoprotein IX platelet, encodes a subunit of a platelet surface membrane glycoprotein complex. This complex functions as a receptor for von Willebrand factor, initiating the maintenance of hemostasis after injury [1,2,3,6]. Variants in human GP9 are associated with Bernard-Soulier syndrome (BSS), a rare autosomal recessive condition characterized by low platelet count and platelet dysfunction [1,2,3,4,5,6]. Animal models, such as the zebrafish gp9SMU15 mutant created using CRISPR-Cas9 technology, help understand the roles and underlying mechanisms of GP9 in thrombopoiesis [3].

In Cocker Spaniel dogs with a mild to severe bleeding disorder resembling human BSS, a 2460-bp deletion in the GP9 gene was identified. This deletion includes a significant part of the single coding exon, resulting in a frameshift and premature stop codon, truncating almost two-thirds of the encoded protein. PCR-based genotyping confirmed recessive inheritance, and the homozygous variant genotype was not seen in 98 control Cocker Spaniels, indicating this variant was likely causative for the BSS-phenotype in these dogs [1]. In a five-year-old girl, a novel variant of the GP9 gene led to BSS type C with easy bruising as the main symptom [2]. Two previously unreported GP9 variants in a BSS patient may modify the conformation of GP-IX interactions and proper expression of the Ib-IX-V complex on platelet membranes [6].

In conclusion, GP9 is crucial for normal platelet function and hemostasis. Genetic variants in GP9 can lead to BSS in both humans and animals. The study of GP9 in animal models, like the Cocker Spaniel dogs and zebrafish, provides valuable insights into the pathogenesis of BSS and may facilitate the development of diagnostic methods and therapeutic strategies for this inherited platelet disorder.

References:

1. Gentilini, Fabio, Turba, Maria Elena, Giancola, Fiorella, Drögemüller, Michaela, Drögemüller, Cord. 2019. A large deletion in the GP9 gene in Cocker Spaniel dogs with Bernard-Soulier syndrome. In PloS one, 14, e0220625. doi:10.1371/journal.pone.0220625. https://pubmed.ncbi.nlm.nih.gov/31484196/

2. Alasmari, Badriah G, Alqahtani, Sameer M, Alabbas, Ali, Alrezqi, Wafa A, Al-Tala, Saeed M. 2024. A Novel Variant of GP9 Gene Resulting in Bernard-Soulier Syndrome: A Case Report. In Cureus, 16, e76363. doi:10.7759/cureus.76363. https://pubmed.ncbi.nlm.nih.gov/39867007/

3. Lin, Qing, Zhou, Riyang, Meng, Panpan, Shi, Linjuan, Zhang, Yiyue. 2022. Establishment of a Bernard-Soulier syndrome model in zebrafish. In Haematologica, 107, 1655-1668. doi:10.3324/haematol.2021.278893. https://pubmed.ncbi.nlm.nih.gov/34407604/

4. Ghalloussi, Dorsaf, Rousset-Rouvière, Caroline, Popovici, Cornel, Alessi, Marie-Christine, Baccini, Véronique. 2020. Bernard-Soulier syndrome: first human case due to a homozygous deletion of GP9 gene. In British journal of haematology, 188, e87-e90. doi:10.1111/bjh.16374. https://pubmed.ncbi.nlm.nih.gov/32030720/

5. Ferrari, Silvia, Regazzo, Daniela, Cerbo, Anna, Bertomoro, Antonella, Simioni, Paolo. 2024. The compound pathogenic effects of a homozygous frameshift variant in the transmembrane region of GP9, causing Bernard-Soulier syndrome, with a missense variant in GP1BB. In British journal of haematology, 205, 742-745. doi:10.1111/bjh.19593. https://pubmed.ncbi.nlm.nih.gov/38923496/

6. Boisseau, P, Debord, C, Eveillard, M, Béné, M C, Fouassier, M. 2017. Two novel variants of uncertain significance in GP9 associated with Bernard-Soulier syndrome: Are they true mutations? In Platelets, 29, 316-318. doi:10.1080/09537104.2017.1371288. https://pubmed.ncbi.nlm.nih.gov/29119855/