Compound Heterozygosity for Silent Cap +1570 (T>C) (HBB: - PDF document

Hemoglobin international journal for hemoglobin research ISSN: 0363-0269 (Print) 1532-432X (Online) Journal homepage: http://www.tandfonline.com/loi/ihem20 Compound Heterozygosity for Silent Cap +1570 (T>C) (HBB: c*96T>C), Codon 39 (C>T) ( HBB : c.118C>T) and the Presence of ααα anti–3.7 / αα in Greece. A Case Presentation Stamatia Theodoridou, Timoleon-Achilleas Vyzantiadis & Efthymia Vlachaki To cite this article: Stamatia Theodoridou, Timoleon-Achilleas Vyzantiadis & Efthymia Vlachaki (2018): Compound Heterozygosity for Silent Cap +1570 (T>C) (HBB: c*96T>C), Codon 39 (C>T) ( HBB : c.118C>T) and the Presence of ααα anti–3.7 / αα in Greece. A Case Presentation, Hemoglobin, DOI: 10.1080/03630269.2018.1495648 To link to this article: https://doi.org/10.1080/03630269.2018.1495648 Published online: 12 Sep 2018. Submit your article to this journal Article views: 7 View Crossmark data Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ihem20

HEMOGLOBIN https://doi.org/10.1080/03630269.2018.1495648 SHORT COMMUNICATION Compound Heterozygosity for Silent Cap 1 1570 (T > C) (HBB: c*96T > C), Codon 39 (C > T) ( HBB : c.118C > T) and the Presence of aaa anti – 3.7 / aa in Greece. A Case Presentation Stamatia Theodoridou a , Timoleon-Achilleas Vyzantiadis b and Efthymia Vlachaki c a Haemoglobinopathy Prevention Unit, Hippokration Hospital of Thessaloniki, Thessaloniki, Greece; b First Department of Microbiology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece; c Adult Thalassemia Unit, Second Department of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece ABSTRACT ARTICLE HISTORY The rare point mutation Cap þ 1570 (T > C) ( HBB : c � 96T > C) has been reported in families of Czech, Received 17 April 2018 Revised 8 June 2018 Greek, Turkish and Italian origin. The mutation contributes to a reduction of the b -globin chain synthe- Accepted 10 June 2018 sis, and in heterozygous carriers, it causes a silent phenotype, while in compound heterozygosity with severe b -thalassemia ( b -thal) mutations, it leads to a non transfusion dependent b -thal intermedia KEYWORDS ( b -TI) state. We report a case of compound heterozygosity for codon 39 (C > T) ( HBB : c.118C > T) and b -Thalassemia intermedia Cap þ 1570, in addition to the presence of aaa anti – 3.7 / aa . ( b -TI); genetic counseling; silent mutation b -Thalassemia ( b -thal) is one of the most extensively studied Thessaloniki, Greece, for further investigation due to genetic diseases with remarkably different clinical pheno- worsening of her anemia. As a child, growth and develop- types. The molecular basis of the phenotypic diversity of ment were satisfactory and presented neither bone deform- b -thal is reported in existing databases [1]. Understanding ities nor thalassemic facies. She had been followed up since the relationship between genotype and phenotype is very her youth with the clinical phenotype of b -TI with the need beneficial in clinical practice for the appropriate treatment of occasional blood transfusions during pregnancy and infec- in homozygous or compound heterozygous patients as well tions (six units). as for the prediction of the phenotype in genetic counseling At presentation, clinical examination revealed splenomeg- of at-risk couples. aly with a longitudinal measure of 220 mm (normal The very rare point mutation Cap þ 1570 (T > C) (HBB : < 130 mm) and extramedullary hematopoiesis with a paraspi- c � 96T > C) has been reported in families of Czech [2], nal mass of 3 cm. Hematological findings of the proband Greek [3], Turkish [4] and Italian [5] origin. The mutation were as follows: hemoglobin (Hb): 8.2 g/dL, hematocrit [or contributes to a reduction of the b -globin chain synthesis. packed cell volume (PCV)]: 0.27 L/L, mean cell volume In heterozygous carriers, it causes a silent phenotype, while (MCV) 69.0 fL, mean cell Hb (MCH) 21.0 pg, while high in compound heterozygosity with severe b -thal mutations, it performance liquid chromatography (HPLC) variant analysis leads to a b -thal intermedia ( b -TI) state. showed Hb A 2 : 5.1% and Hb F: 19.0%. Severe anisocytosis, The coinheritance of the silent Cap þ 1570 defect and severe microcytosis, basophilic stippling and erythroblasts (25.0%) b -thal mutations has been previously reported in Italy by were noted in her blood smear. Her ferritin levels before Vinciguerra et al. [5]. Although the phenotypic and molecular blood transfusion were of 800.0 ng/mL and liver magnetic resonance imaging (MRI) T2 � was 4.7 msec (normal value variety of compound heterozygosity for thalassemic genes is excessive in Greece, to the best of our knowledge, only seven < 6.3 msec), liver iron concentrate (LIC) 11 mgr/g dry weight and heart MRI T2 � 33 msec (normal values > 20 cases of Cap þ 1570 have been reported in Greece [3]. We report the first observed case of a compound heterozygosity for msec). Bone marrow examination showed erythro- codon 39 (C > T) ( HBB : c.118C > T) and Cap þ 1570, in addi- blastic reaction. tion to the presence of aaa anti – 3.7 / aa in a Greek patient. Molecular examination showed that she carried the codon 39 mutation and Cap þ 1570, in addition to the presence of aaa anti – 3.7 / aa . Compound heterozygosity for Case report aaa anti – 3.7 / aa Cap þ 1570 and was found in her A 51-year-old Greek female, with a history of b -TI presented mother and compound heterozygosity for codon 39 and aaa anti – 3.7 / aa was also found in both her father and her at the Thalassaemia Unit, Hippokration Hospital of Thessaloniki, CONTACT Stamatia Theodoridou, MD, PhD hmesogiaki@ippokratio.gr Haemoglobinopathy Prevention Unit, Hippokration Hospital of Thessaloniki, Konstantinoupoleos 48, 54649 Thessaloniki, Greece � 2018 Informa UK Limited, trading as Taylor & Francis Group