Hb H Disease Results from Compound Heterozygosity of – –SEA and –αMAL3.5 in a Chinese Family
Hb H Disease Results from Compound Heterozygosity of – –SEA and –αMAL3.5 in a Chinese Family
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DOI：
10.1080/03630269.2019.1575849
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发表时间：
2019-01
期刊：
影响因子：
1
通讯作者：
Ying Zhao;J. Lou;Manna Sun;Youqing Fu;Wan-Ling Ye;Yanjin Li;Yunshi Dai;Yanhui Liu
中科院分区：
文献类型：
--
作者：
Ying Zhao;J. Lou;Manna Sun;Youqing Fu;Wan-Ling Ye;Yanjin Li;Yunshi Dai;Yanhui Liu
摘要 通过多重连接依赖探针扩增（MLPA），接着进行缺口聚合酶链反应（gap - PCR）和测序，在一个中国家庭中鉴定出一种3.557 kb的α⁺ - 地中海贫血缺失（NG_000006.1: g.32745_36301del，–αMAL3.5），该缺失涉及整个α2 - 珠蛋白基因。先证者是这种突变基因和东南亚缺失（– –SEA；NG_000006.1: g.26264_45564del19301）的复合杂合子，具有血红蛋白H病的表型[血红蛋白（Hb）7.6 g/dL，平均红细胞体积（MCV）60.0 fL，血红蛋白H（β4）0.7%，血红蛋白Bart’s（γ4）2.4%，血红蛋白A2 1.1%]；她的一个具有相同基因型的姐妹表现出相似的表型。另外两名家族成员是这种突变基因的携带者，具有静止型α - 地中海贫血的血液学表型。这种缺失的5'和3'断点分别位于Y2和Y1框，因此，它可能源于这两个同源框之间的不等交换。这种突变构成了中国人群中导致α - 地中海贫血的另一种异质性缺陷，对于阐明人类α - 珠蛋白基因簇的排列具有重要价值。
Abstract The α+-thal deletion of 3.557 kb (NG_000006.1: g.32745_36301del, –αMAL3.5), involving the entire α2-globin gene, was identified in a Chinese family by multiplex ligation-dependent probe amplification (MLPA) followed by gap-polymerase chain reaction (gap-PCR) and sequencing. The proband, a compound heterozygote for this mutant gene and the Southeast Asian (– –SEA; NG_000006.1: g.26264_45564del19301) deletion, had a phenotype of Hb H disease [hemoglobin (Hb) 7.6 g/dL, mean corpuscular volume (MCV) 60.0 fL, Hb H (β4) 0.7%, Hb Bart’s (γ4) 2.4% and Hb A2 1.1%]; one of her sisters with same genotype showed a similar phenotype. Another two family members, who were carriers of this mutant gene, had a hematological phenotype of a silent α-thal. The 5' and 3' breakpoints of this deletion are located at the Y2 and Y1 boxes, respectively, therefore, it probably originated from an unequal crossover between these two homologous boxes. This mutation constitutes an additional heterogeneous defect causing α-thal in the Chinese population and would be valuable for elucidating the arrangement in the human α-globin gene cluster.