Molecular Biology and Biotechnology Department, Human Genetics Division, Atomic Energy Commission of Syria, P.O. Box 6091, Damascus, Syria.
BMC Pediatr. 2019 Feb 18;19(1):61. doi: 10.1186/s12887-019-1435-5.
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).
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 codon 5 [-CT] (HBB: c.17_18delCT) mutation in beta-globin (β-globin) gene and δ 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.
To our knowledge, this is the first report of beta thalassemia intermedia due to combination of Hb Knossos /codon 5 [-CT] associated with δ 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.
β 地中海贫血（β-thal）是一种遗传性血红蛋白疾病，其特征是血红蛋白合成减少，导致小细胞低色素性贫血。β 地中海贫血中间型（TI）是介于携带者状态和重型β 地中海贫血（β-TM）之间的一种临床中间严重程度的术语。
我们描述了一名来自叙利亚西南部库奈特拉省的 12 岁男性先证者。血液学检查显示苍白和贫血（Hb 9g/dl）。平均细胞体积（MCV）为 64fL；平均细胞血红蛋白（MCH）为 21.8pg。毛细管电泳（CE）电泳图显示 Hb A1 水平低（36.2%），Hb F 水平高（62.2%），Hb A2 水平低（1.6%）。该先证者偶尔需要输血。使用直接 DNA 测序和聚合酶链反应-限制性片段长度多态性（PCR/RFLP）检测突变。分子分析显示存在罕见的β Hb Knossos 密码子 27（G>T）（HBB：c.82G>T）变体，与β-球蛋白（β-globin）基因中的β密码子 5[-CT]（HBB：c.17_18delCT）突变和δ-球蛋白（δ-globin）基因中的δ密码子 59[-A]（HBD：c.179delA）突变有关。该先证者对常见的α地中海贫血（α-thal）缺失形式检测呈阴性。Xmn-I 基因座（HBG2：c.-211C>T）多态性显示先证者 Xmn-1 基因座纯合[TT]。
据我们所知，这是首例在叙利亚患者中发现由 Hb Knossos/codon 5[-CT]与 δ codon 59[-A]组合引起的β 地中海贫血中间型病例。另一方面，在叙利亚，由于δ 链生成减少而导致 Hb A2 水平降低的β 地中海贫血携带者，必须筛选不同的 δ-thal 基因突变，以避免β-thal 疾病的误诊。
