Codon 104(-G), a dominant β -thalassemia-like phenotype in a German Caucasian family is associated with mild chronic hemolytic anemia but influenced in severity by co-inherited genetic factorsCodon 104(-G), a heterozygous frameshift mutation in exon 2 of HBB, resulted in a dominantly inherited β 0 -phenotype with mild anemia in a German kindred, and thalassemia intermedia in the index patient. A co-inherited α gene triplication, long-term transfusion therapy, and ineffective erythropoiesis were confounding factors. Haematologica 2007; 92:1264 92: -1265 We report a β 0 -thalassemia deletion mutation with dominant mode of inheritance in a German Caucasian family of Huguenot descent (Figure 1). The proposita (IV-5) presented in our hospital (2002) with hepatosplenomegaly and a Thalassemia intermedia phenotype. Erythrocytes had been previously transfused to her (300 units) and her brother (IV-2, 500 units). Her brother died of malignant melanoma in 2003. Transfusion therapy was continued in the proposita up to the time, when iron overload became evident. From 1999, she had been treated with erythropoietin and iron chelation therapy. Her sister (IV-7) and daughter (V-4) presented with mild chronic hemolytic anemia. Elevated HbA2 (3.9-5.1%) and HbF-levels (3.8 and 5.1%) in the proposita and her daughter (V-4) were detected by high performance liquid chromatography on an ÄKTA Tm basic 10A system (Amersham Biosciences, Freiburg). Low values for Hb (7.7-11.2 g/dL), Hct (28-35%), MCV (69-73.2 fl) and MCH (22.1-24.2 pg) indicated hypochromic anemia (Table 1). Erythrocyte enzyme activities for glycolysis and pentose phosphate cycle were normal. Elevated serum concentrations of iron (39.3 µmol/L), ferritin (2016 µg/L) and a transferrin saturation of 89.8% denoted iron overload and/or hemochromatosis in the proposita. Ultrasonography and computerized tomography showed increased hepatic density, a clinical sign of iron overload. The absence of aberrant or unstable hemoglobin fraction in biochemical Hb analyses together with a thalassemia-like clinical picture suggested β 0 -thalassemia. Informed consent was given for genetic analyses. DNA extraction and polymerase chain reaction (PCR) analysis were performed using standard methods, sequencing with a CEQ Quick Start Kit on a CEQ 8800 automated DNA Sequencer (Beckman Coulter, Krefeld). Primers and PCR conditions are available from the authors upon request. The family members were heterozygous for a β-thalassemia mutation [codon 104 (-G)] at the exon2/IVS-II boundary within a homonucleotide run of three guanines (494-496; -G) ( Figure 2A). The deletion mutant at the end of Figure 1. Pedigree of German kindred shows segregation of dominantly transmitted β β-Thalassemia. The proposita is marked by an arrow; : dead; : dominant Thalassemia; : healthy; : heterozygous; ?: unconfirmed disease. Table 1. Hematological data of four members of German index family (after discontinued transfusion therapy of members IV-2 and IV-5). -1925- F-1933- F-1938- F-1963 94 Both mutation-dependen...