Gallienne Alice E, Iberson Nicola M, Dréau Hélène M, Jackson Helen, Bignell Patricia A, Old John M, Schuh Anna, Henderson Shirley J
National Haemoglobinopathy Reference Laboratory, Molecular Haematology, Oxford Radcliffe Hospitals National Health Service Trust, Oxford, Oxfordshire, UK.
Hemoglobin. 2010;34(1):110-4. doi: 10.3109/03630260903554803.
We have identified and characterized a novel beta-globin gene deletion mutation in a family of Afghan ancestry. The proband was a 10-year-old transfusion-dependent female with the phenotype of beta-thalassemia major (beta-TM). DNA sequencing of the beta-globin gene showed no abnormalities. Multiplex ligation-dependent probe amplification (MLPA) showed reduced/absent probe height of the probe covering the 5' end of the beta-globin gene indicating a possible deletion. Gap-polymerase chain reaction (gap-PCR) produced junctional fragments and direct sequencing of the product revealed that the 5' breakpoint was 478 nucleotides upstream of the Cap site and the 3' breakpoint was in the second exon of the beta-globin gene, giving a deletion size of 909 bp. The proband was homozygous and the parents were heterozygous for the deletion. This is the first report of a large beta-thalassemia (beta-thal) deletion mutation in this ethnic group.
我们在一个具有阿富汗血统的家族中鉴定并表征了一种新型的β-珠蛋白基因缺失突变。先证者是一名10岁的依赖输血的女性，具有重型β地中海贫血（β-TM）的表型。β-珠蛋白基因的DNA测序未显示异常。多重连接依赖探针扩增（MLPA）显示覆盖β-珠蛋白基因5'端的探针高度降低/缺失，表明可能存在缺失。缺口聚合酶链反应（gap-PCR）产生连接片段，对产物进行直接测序显示5'断点位于帽位点上游478个核苷酸处，3'断点位于β-珠蛋白基因的第二个外显子中，缺失大小为909 bp。先证者为该缺失的纯合子，父母为杂合子。这是该族群中首次报道的大型β地中海贫血（β-地贫）缺失突变。
