A New Highly Unstable α Chain Variant Causing α⁺‐Thalassemia: Hb Zurich Albisrieden [α59(E8)Gly→Arg (α2)]

Abstract

A new alpha-globin mutation causing persistent mild hypochromic microcytosis and erythrocytosis is described. Hb Zurich Albisrieden [alpha59(E8)Gly-->Arg (alpha2)] is not detected at the protein level and leads to alpha(+)-thalassemia (thal).

Molecular diagnosis of α‐thalassemia in a multiethnic population

“…This mutation is predicted to significantly disrupt the position of a key helix important for oxygen binding. The clinical picture in the α 2 heterozygotes was of a mild hypochromic microcytic anemia . We identified this α 1 mutation in 6 patients, 4 of whom are members of the same family, of Jewish Georgian origin (Table ).…”

“…p.Gly59Arg [HBA1:c. 247G>C], (Figure 2A,F). An equivalent to this mutation in the α 2 gene (Hb Zurich Albisrieden) was previously described by Dutly et al 34 This mutation is predicted to significantly disrupt the position of a key helix important for oxygen binding. The clinical picture in the α 2 heterozygotes was of a mild hypochromic microcytic anemia.…”

HbH disease due to compound heterozygosity for hemoglobins Zürich‐Albisrieden and Sallanches

“…Hb Zürich‐Albisrieden was described in 2004 . The only six prior reports are from Switzerland, China, and Brazil .…”

“…Hb Zürich‐Albisrieden was described in 2004 . The only six prior reports are from Switzerland, China, and Brazil . This hyperunstable Hb causes a thalassemia major phenotype in homozygotes (α ZA α/α ZA α), HbH disease in compound heterozygotes (α ZA α/α T α or α ZA α/‐α), and hypochromic microcytosis with mild erythrocytosis in heterozygotes (α ZA α/αα) …”

Thalassemia major phenotype caused by HB Zürich‐Albisrieden [α2 59(E8) Gly > Arg (HBA2:C.178G > C)] in a Brazilian child

“…Hb Zürich‐Albisrieden (ZA), described for the first time in 2004 in a 38‐year‐old man of Swiss origin, is a very rare and highly unstable α globin variant in which the glycine (Gly) residue at position 59 in the mature peptide (after N‐terminal methionine excision) is replaced by arginine (Arg) as the result of a GGC > CGC substitution at codon 60 of the α2 gene [HBA2:c.178G > C; (p.G60R)] . This variant cannot be detected in peripheral blood, and only some simple and compound heterozygotes (αα/α ZA α and –/α ZA α, respectively) have been described to date in Switzerland and China . We report here a case of Hb ZA in the homozygous state in a Brazilian infant with severe congenital hemolytic anemia and ineffective erythropoiesis.…”