Germline MYOF1::WNK4 and VPS25::MYOF1 Chimeras Generated by the Constitutional Translocation t(17;19)(q21;p13) in Two Siblings With Myelodysplastic Syndrome

Cancer Genomics Proteomics. 2024 May-Jun;21(3):272-284. doi: 10.21873/cgp.20446.


Background/aim: Constitutional chromosomal aberrations are rare in hematologic malignancies and their pathogenetic role is mostly poorly understood. We present a comprehensive molecular characterization of a novel constitutional chromosomal translocation found in two siblings - sisters - diagnosed with myelodysplastic syndrome (MDS).

Materials and methods: Bone marrow and blood cells from the two patients were examined using G-banding, RNA sequencing, PCR, and Sanger sequencing.

Results: We identified a balanced t(17;19)(q21;p13) translocation in both siblings' bone marrow, blood cells, and phytohemagglutinin-stimulated lymphocytes. The translocation generated a MYO1F::WNK4 chimera on the der(19)t(17;19), encoding a chimeric serine/threonine kinase, and a VPS25::MYO1F on the der(17), potentially resulting in an aberrant VPS25 protein.

Conclusion: The t(17;19)(q21;p13) translocation found in the two sisters probably predisposed them to myelodysplasia. How the MYO1F::WNK4 and/or VPS25::MYO1F chimeras, perhaps especially MYO1F::WNK4 that encodes a chimeric serine/threonine kinase, played a role in MDS pathogenesis, remains incompletely understood.

Keywords: MYOF1; MYOF1::WNK4; Myelodysplastic syndrome (MDS); VPS25::MYO1F; WNK4; constitutional chromosomal translocation; t(17;19)(q21;p13).

Publication types

  • Case Reports

MeSH terms

  • Chromosomes, Human, Pair 17 / genetics
  • Chromosomes, Human, Pair 19 / genetics
  • Female
  • Humans
  • Middle Aged
  • Myelodysplastic Syndromes* / genetics
  • Myelodysplastic Syndromes* / pathology
  • Oncogene Proteins, Fusion / genetics
  • Protein Serine-Threonine Kinases / genetics
  • Siblings*
  • Translocation, Genetic*
  • Vesicular Transport Proteins / genetics


  • Protein Serine-Threonine Kinases
  • Vesicular Transport Proteins
  • Oncogene Proteins, Fusion