1. Double Heterozygosity for Hb Durham-N.C. ( HBB : c.344T>C) [β114(G16)Leu→Pro] and the IVS-I-110 ( HBB : c.93-21G>A) Causing a Severe β-Thalassemia Phenotype.
- Author
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Cannata M, Cassarà F, Vinciguerra M, Licari P, Passarello C, Leto F, Lo Pinto C, Pitrolo L, Ganci R, Maggio A, and Giambona A
- Subjects
- Biomarkers, DNA Mutational Analysis, Erythrocyte Indices, Female, Humans, Infant, beta-Thalassemia blood, Alleles, Amino Acid Substitution, Heterozygote, Mutation, Phenotype, beta-Globins genetics, beta-Thalassemia diagnosis, beta-Thalassemia genetics
- Abstract
The evaluation of a 10-month-old girl of Sicilian origin with a clinical phenotype of severe thalassemia led to the identification of two β-globin gene defects, a β-thalassemia (β-thal), mutation at IVS-I-110 ( HBB : c.93-21G>A) and a variant hemoglobin (Hb) mutation at codon 114 ( HBB : c.344T>C) on the other allele, reported as Hb Durham-N.C. (also known as Hb Brescia) [β114(G16)Leu→Pro] in the HbVar database. A very low Hb level (Hb 3.5 g/dL), microcytosis [mean corpuscular volume (MCV) 63.2 fL] and hypocromia [mean corpuscular Hb (MCH) 19.6 pg], increased red blood cell (RBC) distribution width (RDW) (36.0%), higher reticulocytes (6.2%), anisocytosis, poikilocytosis, hypocromia, basophilic stippling and inclusion body formation, were present in the affected subject. Analysis of other family components showed the presence of HBB : c.93-21G>A defect in the mother and in her brother, while Hb Durham-N.C. was absent in all other relatives, thus, this mutation has arisen as a de novo defect. This is the first case described as a severe thalassemic phenotype in a compound heterozygote carrier of this unstable Hb and a common β-thalassemic allele. The important information gained from this case is that a rare dominant or recessive mutation may arise in every individual, even if this is a very rare event.
- Published
- 2019
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