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

• Published in: Blood cells, molecules, & diseases molecules, & diseases, 2020-11, Vol.85, p.102479-102479, Article 102479
• Main Authors: Chandrasekhar, Chodimella, Pasupuleti, Santhosh Kumar, Sarma, Potukuchi Venkata Gurunadha Krishna
• Format: Article
• Language: English
• Subjects: Congenital erythrocytosis; EEC; EPAS1; EPO-R; VHL
• ISSN: 1079-9796; 1096-0961
• DOI: 10.1016/j.bcmd.2020.102479

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. •Novel mutations identified in EPO-R, VHL and EPAS1 genes were found to be pathogenic.•34.14% were diagnosed to have CE showing positivity for EEC.•In our study, 57.1% of young individuals with erythrocytosis and stroke had CE.•25% of all CE patients had thrombotic events both cardiovascular and neurological.