Torres Lidiane S, Okumura Jéssika V, Belini-Júnior Édis, Oliveira Renan G, Nascimento Patrícia P, Silva Danilo G H, Lobo Clarisse L C, Oliani Sonia M, Bonini-Domingos Claudia R
a Laboratory of Hemoglobin and Hematologic Genetic Diseases , São Paulo State University (UNESP) , São Paulo , Brazil.
b Clinical Hematology Division , Institute of Hematology Arthur de Siqueira Cavalcanti (HEMORIO) , Rio de Janeiro , Brazil.
Hemoglobin. 2016 Sep;40(5):356-358. doi: 10.1080/03630269.2016.1222295. Epub 2016 Oct 3.
Phenotypic heterogeneity for sickle cell disease is associated to several genetic factors such as genotype for sickle cell disease, β-globin gene cluster haplotypes and Hb F levels. The coinheritance of Hb S (HBB: c.20A > T) and Hb D-Punjab (HBB: c.364G > C) results in a double heterozygosity, which constitutes one of the genotypic causes of sickle cell disease. This study aimed to assess the phenotypic diversity of sickle cell disease presented by carriers of the Hb S/Hb D-Punjab genotype and the Bantu [- + - - - -] haplotype. We evaluated medical records from 12 patients with sickle cell disease whose Hb S/Hb D-Punjab genotype and Bantu haplotype were confirmed by molecular analysis. Hb S and Hb D-Punjab levels were quantified by chromatographic analysis. Mean concentrations of Hb S and Hb D-Punjab were 44.8 ± 2.3% and 43.3 ± 1.8%, respectively. Painful crises were present in eight (66.7%) patients evaluated, representing the most common clinical event. Acute chest syndrome (ACS) was the second most prevalent manifestation, occurring in two individuals (16.7%). Three patients were asymptomatic, while another two exhibited greater diversity of severe clinical manifestations. Medical records here analyzed reported a significant clinical diversity in sickle cell disease ranging from the absence of symptoms to wide phenotypic variety. The sickle cell disease genotype, Bantu haplotype and hemoglobin (Hb) levels did not influence the clinical diversity. Thus, we concluded that the phenotypic variation in sickle cell disease was present within a specific genotype for disease regardless of the β-globin gene cluster haplotypes.
镰状细胞病的表型异质性与多种遗传因素相关，如镰状细胞病的基因型、β-珠蛋白基因簇单倍型和胎儿血红蛋白（Hb F）水平。Hb S（HBB: c.20A > T）和Hb D-旁遮普（HBB: c.364G > C）的共同遗传导致双重杂合性，这是镰状细胞病的基因型病因之一。本研究旨在评估Hb S/Hb D-旁遮普基因型和班图[- + - - - -]单倍型携带者所呈现的镰状细胞病的表型多样性。我们评估了12例镰状细胞病患者的病历，这些患者的Hb S/Hb D-旁遮普基因型和班图单倍型经分子分析得以确认。通过色谱分析对Hb S和Hb D-旁遮普水平进行定量。Hb S和Hb D-旁遮普的平均浓度分别为44.8 ± 2.3%和43.3 ± 1.8%。在接受评估的8例（66.7%）患者中出现了疼痛性危象，这是最常见的临床事件。急性胸综合征（ACS）是第二常见的表现，发生在2例个体（16.7%）中。3例患者无症状，而另外2例表现出更广泛的严重临床表现多样性。此处分析的病历报告了镰状细胞病从无症状到广泛表型多样的显著临床多样性。镰状细胞病基因型、班图单倍型和血红蛋白（Hb）水平并未影响临床多样性。因此，我们得出结论，无论β-珠蛋白基因簇单倍型如何，镰状细胞病的表型变异存在于特定的疾病基因型内。
