β‐thalassemia alleles and unstable hemoglobin types among russian pediatric patients

Abstract

A recently initiated collaboration between Russian and American institutions has resulted in the characterization of several known or new beta-thalassemia alleles and unstable hemoglobin types. Nine known beta-thalassemia alleles were present which have also been found in Mediterranean, East Asian, and Black populations; the possibility of independent mutations for some of the rare alleles should be considered. Hb Durham-N.C./Brescia with a codon 114 (CTG-->CCG; Leu-->Pro) change was present in six members of two families. This condition and two new variants have the characteristics of a dominant type of beta-thalassemia heterozygosity with moderate anemia, Heinz body formation, splenomegaly, etc. One new beta-thalassemia allele is a frame-shift at codon 124 (-A), while another is characterized by the introduction of an extra proline residue (codon: CCA) between residues Thr (beta 123) and Val (beta 126) to give the sequence -Thr-Pro-Pro-Pro-Val-.

Dominant inherited β‐thalassemia intermedia in a Polish family due to a novel frameshift mutation in HBB

“…12 A single nucleotide deletion in exon 3 of HBB (c.375delA, p.(Pro126Glnfs*33)) causing dominant β-thalassemia intermedia and hematological findings similar to those in our patients have been described previously in a Russian male (Hb 5-8 g/dL; reticulocytes 1%-3.5%; HbA2 3.9%, HbF 3.0%). 5,6 Except for Pro125, which is changed to histidine in our family, the C-terminal ends of This case illustrates that HBB sequencing in patients with dyserythropoietic anemia can be helpful for diagnosis, even though the patients' ethnicity is not suggesting β-thalassemia.…”

“…A single nucleotide deletion in the same codon 124 of HBB (c.375delA, HbVar ID 954) was already reported previously, leading as well to a dominant β-thalassemia intermedia phenotype. 5,6 Clinically, the children displayed normal growth and development, but the older two had splenomegaly (Table 1). While the children so far do not require RBC transfusions, the father received up to 10 RBC transfusions during adolescence in Poland, but was never placed on a regular transfusion regimen.…”

“…Raute Sunder-Plassmann 2 Jakob Berner 1,3 Stefan Köhrer 1,3 Petra Zeitlhofer 3,4 Oskar A. Haas 1,4 Julia Riedl 5 Leo Kager 1,3 Christian Sillaber 5 1 Department of Pediatrics and Adolescent Medicine, St. Anna Children's…”