The homozygous VHLD126N missense mutation is associated with dramatically elevated erythropoietin levels, consequent polycythemia, and early onset severe pulmonary hypertension

Pediatric Blood and Cancer

Volumn 61, Issue 11, 2014, Pages 2104-2106

  Sarangi, Susmita ^a   Lanikova, Lucie ^b,c   Kapralova, Katarina ^b,c   Acharya, Suchitra ^a   Swierczek, Sabina ^b   Lipton, Jeffrey M ^a   Wolfe, Lawrence ^a   Prchal, Josef T ^b,d  

^a Northwell Health   (United States)

^b UNIVERSITY OF UTAH SCHOOL OF MEDICINE   (United States)

^c PALACKÝ UNIVERSITY   (Czech Republic)

^d VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

Erythropoietin; Polycythemia; Pulmonary hypertension; Von Hippel Lindau gene

Indexed keywords

DALTEPARIN; ERYTHROPOIETIN; GENOMIC DNA; HEMOGLOBIN; IRON; NITRIC OXIDE; VON HIPPEL LINDAU PROTEIN; EPO PROTEIN, HUMAN; VHL PROTEIN, HUMAN;

ANTICOAGULANT THERAPY; ARTICLE; ARTIFICIAL VENTILATION; BRAIN STEM INFARCTION; CASE REPORT; DISEASE SEVERITY; ETHNICITY; EXON; FAILURE TO THRIVE; GENE SEQUENCE; GENERAL CONDITION DETERIORATION; GENETIC ASSOCIATION; HEART CATHETERIZATION; HEMATOCRIT; HEMOGLOBIN BLOOD LEVEL; HOMOZYGOTE; HUMAN; INFANT; LIVER HEMANGIOMA; MALE; MISSENSE MUTATION; NUCLEAR MAGNETIC RESONANCE IMAGING; PARAINFLUENZA VIRUS INFECTION; PHLEBOTOMY; POLYCYTHEMIA; PRIORITY JOURNAL; PULMONARY HYPERTENSION; RESPIRATORY DISTRESS; SEIZURE; THROMBOSIS; THROMBOSIS PREVENTION; BLOOD; GENETICS;

ERYTHROPOIETIN; HUMANS; HYPERTENSION, PULMONARY; INFANT; MALE; MUTATION, MISSENSE; POLYCYTHEMIA; VON HIPPEL-LINDAU TUMOR SUPPRESSOR PROTEIN;

EID: 84918528477     PISSN: 15455009     EISSN: 15455017     Source Type: Journal    
DOI: 10.1002/pbc.25056     Document Type: Article

References (13)

1. Ang SO, Chen H, Hirota K, et al. Disruption of oxygen homeostasis underlies congenital Chuvash polycythemia. Nat Genet 2002; 32:614-621.
2. Ljubas T, Piterkova L, Huff C, et al. Polycythemia due to Croatian homozygous VHL (571c>G:H191D) mutation has a different phenotype than Chuvash polycythemia (VHL 598C>T:R200W). Haematologica 2013; 98:560-567.
3. Lanikova L, Lorenzo F, Yang C, et al. Novel homozygous VHL mutation in exon 2 is associated with congenital polycythemia but not with cancer. Blood 2013; 121:3918-3924.
4. Pastore YD, Jelinek J, Ang S, et al. Mutations in the VHL gene in sporadic apparently congenital polycythemia. Blood 2003; 101:1591-1595.
5. Pastore Y, Jedlickova K, Guan Y, et al. Mutations of von Hippel-Lindau tumor-suppressor gene and congenital polycythemia. Am J Hum Genet 2003; 73:412-419.
6. Bond J, Gale DP, Connor T, et al. Dysregulation of the HIF pathway due to VHL mutation causing severe erythrocytosis and pulmonary arterial hypertension. Blood 2011; 117:3699-3701.
7. Bento MC, Chang KT, Guan Y, et al. Congenital polycythemia with homozygous and heterozygous mutations of von Hippel-Lindau gene: Five new Causcasian patients. Haematologica 2005; 90:128-129.
8. Lorenzo FR, Yang C, Lanikova L, et al. Novel compound VHL heterozygosity (VHL T124A/L188V) associated with congenital polycythaemia. Br J Haematol 2013; 162:851-853.
9. Cario H, Schwarz K, Jorch N, et al. Mutations in the von Hippel-Lindau (VHL) tumor suppressor gene and VHL-haplotype analysis in patients with presumable congenital erythrocytosis. Haematologica 2005; 90:19-24.
10. Randi ML, Murgia A, Putti MC, et al. Low frequency of VHL gene mutations in young individuals with polycythemia and high serum erythropoietin. Haematologica 2005; 90:689-691.
11. Kapralova K, Lanikova L, Lorenzo F, et al. RUNX1 and NF-E2 upregulation is not specific for MPNs, but is seen in polycythemic disorders with augmented HIF signaling. Blood 2014; 123:391-394.
12. Hartfield DS, Lowry NJ, Keene DL, et al. Iron deficiency: A cause of stroke in infants and children. Pediatr Neurol 1997; 16:50-53.
13. Bushuev VI, Miasnikova GY, Sergueeva AI, et al. Endothelin-1, vascular endothelial growth factor and systolic pulmonary artery pressure in patients with Chuvash polycythemia. Haematologica 2006; 91:744-749.