Two different mutations in codon 97 of the β-globin gene cause Hb Malmö in Sweden

Abstract

An abnormal hemoglobin with increased oxygen affinity, Hb Malmö [alpha 2 beta 297(FG4)His-->Gln], was found to cause erythrocytosis in two apparently unrelated Swedish families. Direct nucleotide sequencing of amplified DNA demonstrated a CAC-->CAA substitution in one family and a CAC-->CAG substitution in the other. Both mutations resulted in a His-->Gln substitution in codon 97. This finding prompted us to examine the possible point mutations underlying the different hemoglobin variants reported in the literature.

Hb Malmö [β-97(FG-4)His→Gln] leading to polycythemia in a Dutch family

“…Recently, a second Swedish Hb Malmö family has been described in which the amino acid substitution His]Gln at position b-97 was coded by a CAA triplet [14]. Investigation at the DNA level in one of the carriers from the first Swedish family revealed that the same His]Glu substitution at position b-97 was coded by a CAG codon.…”

At high altitude in the Netherlands: secondary erythrocytosis due to HB-Malmö

“…It is an autosomal dominant congenital disorder located on a gene at chromosome 11, in the B-chain on codon 97, decoding the α-subunit and β-subunit of the haemoglobin 3. Two different mutations have been described (CAC→CAA and CAC→CAG) by which histidine is replaced by glutamine 4. This change in amino acid causes a disorder in the connection between the α1-subunit and β2-subunit of the haemoglobin structure.…”

“…In the international literature, 10 families or single cases have been described with Hb-Malmö 2 4 6 7 – 15…”