A Screening Approach for Inherited Erythrocytosis due to the VHL:c.598C   & gt;  T Mutation (Chuvash Polycythemia)

AbstractGenetic work-up of unexplained erythrocytosis that is suspected to be inherited in nature currently requires either laborious exon-by-exon gene panel testing by Sanger sequencing or expensive next-generation sequencing. A high prevalence of Chuvash polycythemia (61%) has been previously reported among north Indian erythrocytosis patients. We assessed PCR-RFLP forVHL c.598C  >  T mutation as a first-line test in 99 persons withJAK2 V617F-negative, unexplained erythrocytosis.  We enrolled two groups: Group A (n = 38) had erythrocytosis patients (n = 33) or their first-degree relatives (n = 5), and, Group B with 61 healthy blood donation volunteers who were deferred after the discovery of unexplained high hemoglobin levels. Detailed history and clinical exami nation, hemogram, erythropoietin levels and PCR–RFLP for theVHL:c.598C  >  T;p.R200W mutation were done. In Group A, three (8%) persons aged 9, 13 and 30-years were homozygous forVHL:c.598C  >  T. Two were heterozygous (parents of a known case of Chuvash polycythemia). None of the Group B subjects had the Chuvash mutation. Erythropoietin levels in group A were low in 5/26 cases (19%) and normal in 18/26 (69%). In Group B, seven (11%) donors had normal values while the remaining 54 (89%) had high erythropoietin levels. Despite a lower frequency (8%) compared to literature, our results suggest that the relatively simpler PCR-RFLP forVHL:c.598C  >  T mutation may be consider...
Source: Indian Journal of Hematology and Blood Transfusion - Category: Hematology Source Type: research