Hb Yaoundé [β134(H12)Val→Ala] in Association with Hb C [β6(A3)Glu→Lys] in a Caucasian Portuguese Family

Abstract

Hb Yaoundé [β134(H12)Val→Ala] is a rare, silent and asymptomatic hemoglobin (Hb) variant. It was previously reported in a Black man from Cameroon, in association with Hb Kenitra [β69(E13)Gly→Arg], and was subsequently found and described as Hb Mataro in a sub‐Saharan child. To date, Hb Yaoundé has not been described in Caucasian people and molecular studies have never been performed. Here we describe a three‐generation Caucasian Portuguese family in whom Hb Yaoundé was found in association with Hb C [β6(A3)Glu→Lys] (in the proband) and in a heterozygous state (in the proband's mother). The Hb studies of the proband's hemolysate, performed by isoelectric focusing (IEF) and low‐pressure cation exchange chromatography, only revealed an Hb variant identified as Hb C by comparison with a control. However, analysis performed by reversed‐phase high‐performance liquid chromatography (HPLC) showed two different β chain variants and a complete absence of the normal β chain. This uncommon Hb variant was identified as Hb Yaoundé by DNA sequencing analysis of the β‐globin gene (codon 134, GTG→GCG). The β‐globin gene haplotypes were determined in all family members using polymerase chain reaction (PCR)‐based methodology; Hb Yaoundé was found to be associated with the Mediterranean haplotype II. This study is the first description of Hb Yaoundé in Caucasian individuals, and its association with a Mediterranean haplotype supports the hypothesis of an independent genetic origin other than African.