Novel mutations in the EPO-R, VHL and EPAS1 genes in the Congenital Erythrocytosis patients.

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  • Additional Information
    • Source:
      Publisher: Academic Press Country of Publication: United States NLM ID: 9509932 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-0961 (Electronic) Linking ISSN: 10799796 NLM ISO Abbreviation: Blood Cells Mol Dis Subsets: MEDLINE
    • Publication Information:
      Publication: <1996-> : Orlando, FL : Academic Press
      Original Publication: La Jolla, Calif. : Blood Cells Foundation, 1995-
    • Subject Terms:
      Basic Helix-Loop-Helix Transcription Factors/*genetics ; Polycythemia/*congenital ; Receptors, Erythropoietin/*genetics ; Von Hippel-Lindau Tumor Suppressor Protein/*genetics; Adult ; Female ; Frameshift Mutation ; Humans ; Male ; Middle Aged ; Mutation ; Mutation, Missense ; Point Mutation ; Polycythemia/genetics ; Young Adult
    • Abstract:
      Congenital erythrocytosis (CE) can be classified as primary and secondary and 82 consecutive patients of erythrocytosis who were JAK-2 mutation negative, were further investigated. The genomic DNA was extracted from all the patients and the EPO-R, VHL, EGLN1 and EPAS1 genes were PCR amplified and sequenced. The sequence analysis showed (28/82) 34.14% patients had mutations. Among them, (19/28) 67.86% patients had mutations in exon 8 of EPO-R gene, of which six were novel missense mutations, p.(Gly418Ala), p.(Gly390Ala), p.(Ala411Thr), p.(Gly475Val), p.(Glu490Asp), p.(Glu362Gln) and three were novel frameshift mutations, p.(Glu336*), p.(Pro327Hisfs*68), p.(Gly479Alafs*37). All these EPO-R patients were heterozygotes and were forming endogenous erythrocyte colonies (EEC). Some patients (8/28) 28.57% had mutations in VHL gene, out of which 3 novel homozygous missense mutations in exon 1 of VHL gene, p.Gly80Asp, p.Gln107Glu and p.Gln113Glu, were identified. In addition, (1/28) 3.5% patients had one reported heterozygous missense mutation in exon 12 of EPAS1 gene p.Gly537Arg and one novel frameshift mutation p.(Ala553Glyfs*58). Further, in silico analysis indicated most of the mutations, probably, were damaging the protein structures, causing the CE in these patients. In this study the mutations in EPO-R and EPAS1 genes were identified for the first time in India.
      Competing Interests: Declaration of competing interest The authors declare no competing interests.
      (Copyright © 2020 Elsevier Inc. All rights reserved.)
    • Contributed Indexing:
      Keywords: Congenital erythrocytosis; EEC; EPAS1; EPO-R; VHL
    • Accession Number:
      0 (Basic Helix-Loop-Helix Transcription Factors)
      0 (Receptors, Erythropoietin)
      1B37H0967P (endothelial PAS domain-containing protein 1)
      EC 2.3.2.27 (Von Hippel-Lindau Tumor Suppressor Protein)
      EC 6.3.2.- (VHL protein, human)
    • Subject Terms:
      Polycythemia, primary familial and congenital
    • Publication Date:
      Date Created: 20200803 Date Completed: 20210527 Latest Revision: 20210527
    • Publication Date:
      20250114
    • Accession Number:
      10.1016/j.bcmd.2020.102479
    • Accession Number:
      32739800