Game Laurence, Bergounioux Jean, Close James Paul, Marzouka B Esperenza, Thein Swee Lay
Department of Haematological Medicine, King's College Hospital, Guy's, Kings' & St Thomas' School of Medicine, King's College London, London, UK.
Br J Haematol. 2003 Oct;123(1):154-9. doi: 10.1046/j.1365-2141.2003.04564.x.
We describe a novel deletion causing (epsilongammadeltabeta) degrees thalassaemia segregating in three generations of a Chilean family of Spanish descent. Heterozygotes for the deletion were all affected by neonatal haemolytic anaemia. The deletion of 152,569 bp extends from 77 kb upstream of the epsilon gene to 31 kb downstream of the beta gene, and includes the entire beta-globin gene cluster and two upstream olfactory receptor genes. Comparison of the sequences of the deletion junction with those of the flanking normal DNA suggests that the deletion results from a non-homologous recombination event. The insertion of 16 'orphan' nucleotides in the deletion junction creates a perfect inverted repeat of 12 nucleotides, forming a 12-bp stem with a four-nucleotide loop that could have contributed to the illegitimate recombination. The 3' breakpoint is located within an L1 family repeat that contains a perfect 160-bp palindrome, and is in close proximity to the 3' breakpoints of five other deletions in the beta cluster - Indian (HPFH-3), Italian (HPFH-4) and Vietnamese GgammaAgamma (deltabeta) degrees HPFH, German and Belgian Ggamma (Alphagammadeltabeta) degrees thalassaemia.
我们描述了一种导致（εγδβ）°地中海贫血的新型缺失，该缺失在一个西班牙裔智利家庭的三代人中呈分离状态。该缺失的杂合子均受新生儿溶血性贫血影响。152,569 bp的缺失从ε基因上游77 kb延伸至β基因下游31 kb，包括整个β珠蛋白基因簇和两个上游嗅觉受体基因。将缺失连接处的序列与侧翼正常DNA的序列进行比较表明，该缺失是由非同源重组事件导致的。缺失连接处插入的16个“孤儿”核苷酸形成了一个12个核苷酸的完美反向重复序列，形成了一个带有四个核苷酸环的12 bp茎，这可能促成了非法重组。3'断点位于一个L1家族重复序列内，该重复序列包含一个完美的160 bp回文序列，并且与β簇中其他五个缺失的3'断点（印度型（HPFH - 3）、意大利型（HPFH - 4）和越南型GγAγ（δβ）°HPFH、德国型和比利时型Gγ（αγδβ）°地中海贫血）非常接近。
