In other species: dog , domestic cat

Categories: Haematopoietic system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 273800 (trait) , 607759 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2006

Cross-species summary: More specifically called Glanzmann thrombasthenia.

Molecular basis: Christopherson et al. (2006) reported a "single guanine to cytosine (CGG to CCG) substitution in codon 41 in exon 2" of ITGA2B that "would result in the substitution of a proline for an arginine in a highly conserved region of the encoded protein" as a likely causal variant in an affected Thoroughbred cross and in an affected Quarter Horse. Noting that the affected Quarter Horse was only heterozygous for this variant, Christopherson et al. (2006) hypothesised that this horse " is likely a compound heterozygote" for this variant and a second yet-to-be-discovered variant. Christopherson et al. (2007) reported that the second variant in the affected Quarter Horse described in 2006 is "a 10-bp deletion including the splice site between exon 11 and intron 11 . . . [that] would be predicted to result in a lack of splicing of intron 11 and inclusion of a premature stop codon 50 bp downstream of the mutation in the incompletely spliced mRNA." Sanz et al. (2011) reported the same 10-bp deletion as being likely causative in a Peruvian Paso mare. Macieira et al. (2011) reported "A point mutation from G to C in exon 2 of ITGA2B causing a substitution of the expected amino acid arginine 72 (Arg(72)) by a proline (Pro(72))" as the likely causal variant for an affected Oldenburg filly, stating that this variant "corresponds" to the variant reported by Christopherson et al. (2006).

Prevalence: Leite et al. (2020) reported that the two known likely causal variants were completely absent from 1053 DNA samples of clinically healthy Quarter Horse (n = 679) and Warmblood horses (n = 374) in Brazil, consistent with the observation that "this disease has not been described in Brazil". Although their samples were of adequate size, the authors rightly concluded that "it is not possible to affirm that there are no horses carrying mutated alleles in Brazil."

Breeds: Oldenburg (Horse) (VBO_0001034), Quarter Horse (Horse) (VBO_0001057), Thoroughbred (Horse) (VBO_0001083).
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: