Figure 1.

Graphical representation of the 18 pedigrees with autosomal dominant inheritance of macrothrombocytopenia in the discovery and validation collections. No genome-wide excess relatedness among individuals subjected to high-throughput sequencing from different pedigrees sharing the same variant (pedigrees B and I, C and J, D and E and H and L) could be detected by genetic analysis,²⁵ although the shared variants in GP1BB may have been co-inherited from a distant common ancestor. Filled symbols: macrothrombocytopenia, grey symbols: unknown, blank symbols: normal platelet count and volume and absence of macrothrombocytes. Squares: males, circles: females, +/M: heterozygous, +/+: wildtype. A second variant encoding L175P was identified by Sanger sequencing in K-3 absent from K-6 which might influence PLT and MPV by affecting the cytoskeleton. The probability of the genotyping results under the null hypothesis of random segregation, conditional on the genotypes of the index cases, is 0.5⁹ = 1.95x10^-3.