Thrombopoietin Measurement as a Key Component in the Evaluation of Pediatric Thrombocytosis.
JAK2, MPL, and CALR mutations, which underlie essential thrombocythemia (ET) in most adults, are infrequent in children. Consequently, additional tests are needed to confirm pediatric ET diagnoses. We report a child with suspected ET and normal JAK2, MPL, and CALR analyses. Serum thrombopoietin (TPO) was markedly elevated, leading to analysis of the TPO gene, TPHO, which contains an upstream open reading frame (uORF) known to repress THPO translation. Sequencing revealed a de novo, germline stopgain mutation in the uORF, explaining the elevated TPO and thrombocytosis. This finding suggests that screening TPO levels and, if elevated, THPO 5' UTR sequencing could be diagnostic.
Medical Scientist Training Program, Baylor College of Medicine, Houston, Texas.
Nya D
ND
Nelson
Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas.|Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
Andrea
A
Marcogliese
Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
Katie
K
Bergstrom
Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
Michael
M
Scheurer
Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
Donald
D
Mahoney
Department of Pediatrics, Baylor College of Medicine, Houston, Texas.|Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, Texas.
Alison A
AA
Bertuch
D037282:Calreticulin / Q000235:genetics*; D006801:Humans; D007223:Infant; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D010976:Platelet Count; D053628:Receptors, Thrombopoietin / Q000235:genetics*; D013920:Thrombocythemia, Essential / Q000175:diagnosis* / Q000235:genetics*; D013926:Thrombopoietin / Q000097:blood* / Q000235:genetics
D037282:Calreticulin; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; D013926:Thrombopoietin; C507924:JAK2 protein, human; D053614:Janus Kinase 2
THPO; essential thrombocythemia; thrombocytosis; thrombopoietin; upstream open reading frame