Unexpected Genotype in a Non-Transfusion Dependent Thalassemia Family

Abstract

Non-transfusion dependent thalassemia (NTDT) is an inherited hemoglobin disorder characterized by an α/non-α globin chain imbalance of variable severity, resulting in a wide spectrum of clinical manifestations. The coinheritance of additional α genes with a beta-thalassemia heterozygous mutation has a well-known negative effect. Triplication or quadruplication alone are mostly found by chance, but the coinheritance with β mutations can worsen the very mild anemia to a more severe hematological and clinical phenotype causing NTDT, depending on the severity of beta mutations. We describe a case of a 38-year-old β-thalassemia trait, pregnant woman at 33 weeks of gestation with supernumerary α-globin genes and two β-globin defects.

Keywords: Genetic counselling; Non-transfusion dependent thalassemia; Supernumerary α-globin genes; α and β-globin defects coinheritance.

Figure 1

Profile of MLPA probemix P140 HBA cluster of the proband carrying a multiplication of HBA genes. The triangles represent the probe ratio of about 2 corresponding to alpha genes quadruplication; the dots represent the probe ratios of about 1.5 corresponding to alpha genes triplication, while the squares correspond to overlapping probes. MLPA: multiplex ligation-dependent probe amplification.