Gupta Amar Das, Nadkarni Anita, Mehta Pallavi, Goriwale Manju, Ramani Manisha, Chaudhary Pradnya, Mehrotra Vishal, Colah Roshan
Department of Hematology, SRL Limited, Mumbai, Maharashtra, India.
Department of Hematogenetics, National Institute of Immunohaematology, Mumbai, Maharashtra, India.
Indian J Pathol Microbiol. 2017 Jan-Mar;60(1):79-83. doi: 10.4103/0377-4929.200030.
Alpha globin chain variants are clinically significant since they directly influence the structure and function of the hemoglobin (Hb) molecules they constitute, either in combination with normal beta globin chains or with variant beta chains, thereby altering the morbidity and mortality associated with the resultant hemoglobinopathies. We describe here two unrelated families from Madhya Pradesh who had a nondeletional alpha-chain variant, HbO Indonesia (CD116 G → A). Members of one of the two families also had coinheritance of sickle hemoglobin (HbS).
The aim was to study the phenotype of HbO Indonesia and its interaction with HbS.
Hb electrophoresis, high-performance liquid chromatography (HPLC), covalent reverse dot blot hybridization, amplification refractory mutation system, multiplex polymerase chain reaction, and direct gene sequencing were used to identify and characterize the variant Hbs.
The abnormal Hb moved in HbS region in Hb electrophoresis at alkaline pH but gave an abnormal peak in HPLC with a retention time (RT) of 4.86-4.89 min. In two members of the family with coinheritance of HbS, it produced small additional abnormal Hb peaks (4.6% in heterozygous and 11.9% in homozygous member) in HPLC with a longer RT (5.15-5.17 min) possibly resulting from a combination of HbO Indonesia alpha chain with HbS beta chain.
It appears that depending on the zygosity of HbS, HbO Indonesia would subtract a variable amount of HbS beta chain from the total pool, thereby potentially reducing the clinical severity of HbS disease. HbO Indonesia per se does not cause anemia or alter the red cell indices.
α珠蛋白链变体具有临床意义，因为它们直接影响由其构成的血红蛋白（Hb）分子的结构和功能，无论是与正常β珠蛋白链结合还是与变体β链结合，从而改变与由此产生的血红蛋白病相关的发病率和死亡率。我们在此描述来自中央邦的两个无血缘关系的家族，他们有一种非缺失型α链变体，即HbO印度尼西亚型（CD116 G→A）。这两个家族中的一个家族的成员还同时遗传了镰状血红蛋白（HbS）。
目的是研究HbO印度尼西亚型的表型及其与HbS的相互作用。
采用血红蛋白电泳、高效液相色谱（HPLC）、共价反向斑点杂交、扩增阻滞突变系统、多重聚合酶链反应和直接基因测序来鉴定和表征变体血红蛋白。
在碱性pH条件下的血红蛋白电泳中，异常血红蛋白迁移至HbS区域，但在HPLC中出现异常峰，保留时间（RT）为4.86 - 4.89分钟。在同时遗传了HbS的家族中的两名成员中，它在HPLC中产生了额外的小异常血红蛋白峰（杂合子中为4.6%，纯合子成员中为11.9%），保留时间更长（5.15 - 5.17分钟），这可能是由于HbO印度尼西亚型α链与HbSβ链结合所致。
看来，根据HbS的纯合状态，HbO印度尼西亚型会从总库中减去可变数量的HbSβ链，从而有可能降低HbS疾病的临床严重程度。HbO印度尼西亚型本身不会导致贫血或改变红细胞指数。
