A Second Observation of the Fetal Methehoglobin Variant HB F-M-Fort Ripley or α₂^Gγ₂⁹²(F8)HIS→TYR

Abstract

We have identified a second baby with the fetal methemoglobin F-M-Fort Ripley. It was observed in a Caucasian infant from Canada; at least eleven additional members of that family were known to have had a neonatal cyanosis similar to that seen in the propositus and in a previously described baby (2). Sequencing of amplified DNA that included (part of) the G_γ gene greatly facilitated the characterization. The G_γx chain was readily isolated by reversed phase high performance liquid chromatography; its quantity was ∼12.5% of total γ. Interestingly, the baby also carried the AγT mutation on one chromosome, either in cis or in trans to the Gγx mutation. Hb F-M-Fort Ripley could be isolated in reasonably pure form by DEAE-cellulose chromatography. The isolated Hb Fx was unstable, had spectral changes characteristic for the M-hemoglobins, while its methemqglobin derivative reacted rapidly with cyanide. Oxygen affinity data could not be obtained. It is suggested that the formation of a rather large amount (∼25%) of mixed hybrids (α₂G_γX.γ) with low oxygen affinity is the main cause for the occurrence of the neonatal cyanosis.