Hb Knossos (HBB: c.82G > T), β-globin CD 5 (−CT) (HBB: c.17_18delCT) and δ-globin CD 59 (−a) (HBD: c.179delA) mutations in a Syrian patient with β-thalassemia intermedia

Abstract

Background Beta thalassemia (β-thal) is an inherited hemoglobin disorder characterized by reduced synthesis of the hemoglobin that results in microcytic hypochromic anemia. β-Thalassemia intermedia (TI) is a clinical term of intermediate gravity between the carrier state and β-thalassemia major (β -TM). Case presentation We describe a 12-year-old male proband originating from Al-Quneitra province - southwest Syria. Hematological investigations revealed, pallor and anemia (Hb 9 g/dl). The mean cell volume (MCV) 64 fL; mean cell hemoglobin (MCH) 21.8 pg. Capillary electrophoresis (CE) electropherogram revealed low level of Hb A1 (36.2%), high level of Hb F (62.2%) and low level of Hb A2 (1.6%). The proband requires blood transfusion occasionally. Direct DNA sequencing and Polymerase chain reaction-restriction fragment length polymorphism (PCR/RFLP) for mutations detection were used. The molecular analysis revealed the presence of rare β + Hb Knossos codon 27 (G > T) (HBB: c.82G > T) variant associated with β 0 codon 5 [−CT] (HBB: c.17_18delCT) mutation in beta-globin (β-globin) gene and δ 0 codon 59 [−A] (HBD: c.179delA) mutation in delta-globin (δ-globin) gene. The proband tested negative for the common deletional forms of alpha thalassemia (α-thal). Polymorphism of the Xmn-I locus (HBG2: c.-211C > T) revealed that the proband had a homozygous [TT] for Xmn-1 locus. Conclusions To our knowledge, this is the first report of beta thalassemia intermedia due to combination of Hb Knossos /codon 5 [−CT] associated with δ 0 codon 59 [−A] in Syrian patient. On the other hand, in Syria, β-thal carriers who have low level of Hb A2 due to decreased δ-chain production, different δ-thal gene mutations must be screened to avoid the failure diagnosis of β-thal disease.

Performance Evaluation of the DxC 700 AU Chemistry Analyzer in Hemoglobin A1c Measurement

“…In case of variant 13, when the molecular analysis result indicated beta-thalassemia caused by a nonsense mutation in HBB, the peak in zone D and the decreased HbA2 concentration could only be explained if the patient also carried a mutation in HBD. Faten, et al [16] reported a similar case in 2019, in which the proband was affected by beta-thalassemia intermedia and also had a mutation in HBD, resulting in an electrogram indicating a low HbA2 concentration. We did not have the appropriate tools to analyze the HBD gene; thus, the presence of an HBD variant could not be verified.…”

“…Faten, et al . [ 16 ] reported a similar case in 2019, in which the proband was affected by beta-thalassemia intermedia and also had a mutation in HBD , resulting in an electrogram indicating a low HbA 2 concentration. We did not have the appropriate tools to analyze the HBD gene; thus, the presence of an HBD variant could not be verified.…”

Генетична Диагностика На Бета-Таласемия В България – Какво Научихме От Нашите Пациенти

“…При представения клиничен случай 1 лабораторни данни за таласемия минор има само при единия родител, докато клиниката на пациента (включително нуждата от хемотрансфузии) не кореспондира с носителски статус. Разкритото с генетичен анализ носителство на HbKnossos при другия родител не се асоциира с клинична симптоматика и не води до промяна в лабораторните показатели от електрофорезата на хемоглобин, което е в съответствие с докладваното в различни бази данни [11][12][13]. Провеждането на генетични изследвания при пробанда и родителите е препоръчително във всички случаи на бета-таласемия и особено полезно при пациенти с нетипична клиника.…”