The high oxygen-affinity Hemoglobin Johnstown [(beta 109(G11) Val-->Leu] in a German kindred with an elevated erythrocyte hemoglobin content: potential interaction with HFE mutations.

A 23-year-old man with an elevated blood hemoglobin was found to have hemoglobin (Hb) Johnstown, a high oxygen-affinity hemoglobin and an elevated red cell hemoglobin content. The hemoglobin mutation was present in all family members who consented to molecular investigation. No elevation of the erythropoietin level was found in the carriers. A high ferritin level was observed in one family member. When carriers of the hemoglobin mutation were analyzed for mutations in the HFE-genes (C282Y, H63D and S65C), only the individual with the high ferritin level was a compound heterozygous for the H63D/S65C genotype. This genotype normally does not confer the hemochromatosis phenotype but may contribute to iron overload when present in an individual with increased hemoglobin synthesis. The original report of this hemoglobin variant was in the United States. Additional descriptions followed from Spain and Argentina. The family in this report is the first described in Central Europe carrying the beta109 (Val-->Leu) mutation.