Identification of the germline mutation causing MPNs in the Australian family and screening in other MPN cases. (A) Family tree of the Australian family. The patients with mutations in JAK2, MPL, and CALR are marked. Below the mutations, the age at diagnosis is indicated. (B) Genomic regions shared by the 3 affected members in the family identified by the segregation exclusion analysis (red horizontal bars). Arrows indicate the physical position of the candidate genes RBBP6, ARMC5, and C20orf3. (C) Validation of the mutations in RBBP6, ARMC5, and C20orf3 segregating with the disease in the pedigree. The locations of mutations are marked with an arrow. (D) The RBBP6 mutations found in familial cases of MPNs. The respective family trees are shown. For both families, DNA was available only from 1 member and the segregation of the mutation with MPN was not possible to establish. (E) The 2 unique RBBP6 mutations found in 3 sporadic cases of MPNs. (F) The schematic structure of the RBBP6 protein with known and predicted domains. The locations of the detected mutations that are not observed in healthy controls are shown with stars. AAS, absence of allele-sharing; BR, binding region; DWNN, domain with no name; Mb, megabase pair; Znf, zinc finger domain.