Gilad Oded, Dgany Orly, Noy-Lotan Sharon, Krasnov Tania, Elitzur Sarah, Pissard Serge, Kventsel Iris, Yacobovich Joanne, Tamary Hannah
Department of Pediatrics B, Schneider Children's Medical Center of Israel , Petah Tikva , Israel .
Hemoglobin. 2014;38(5):319-24. doi: 10.3109/03630269.2014.954668. Epub 2014 Sep 15.
The molecular basis of α-thalassemia (α-thal) is complex. The use of multiplex ligation-dependent probe amplification (MLPA) has offered the possibility of identifying more gene deletions causing α-thal. Our objective was to determine the molecular basis of two patients with Hb H (β4) disease. By using MLPA in combination with comparative genomic hybridization (CGH) we identified two novel α-globin gene cluster deletions: a 30 kb deletion (patient 1) we refer to as - -(JAL) and a large 216 kb deletion (patient 2) we refer to as - -(LOD). Patient 1 was a compound heterozygote for - -(JAL) and -α(3.7) (rightward deletion). Twelve family members of patient 1 carrying the - -(JAL) deletion were available for evaluation: five with - -(JAL)/-α(3.7), four with - -(JAL)/α(Hph I)α and three with - -(JAL)/αα. Their clinical picture of compound heterozygosity was compatible with moderate Hb H disease. In patient 2 (- -(LOD)/-α(3.7)), no additional symptoms were present despite the heterozygous deletion of seven known genes, three non coding RNAs (ncRNAs), four unknown genes and two pseudo genes. Further analysis of more patients with α-thal deletions will have implications for genetic counseling and appropriate therapy.
α地中海贫血（α-thal）的分子基础很复杂。多重连接依赖探针扩增（MLPA）技术为鉴定更多导致α-thal的基因缺失提供了可能。我们的目的是确定两名Hb H（β4）病患者的分子基础。通过将MLPA与比较基因组杂交（CGH）相结合，我们鉴定出两个新的α珠蛋白基因簇缺失：一个30 kb的缺失（患者1），我们将其称为--(JAL)，以及一个216 kb的大片段缺失（患者2），我们将其称为--(LOD)。患者1是--(JAL)和-α(3.7)（向右缺失）的复合杂合子。患者1的12名携带--(JAL)缺失的家庭成员可供评估：5名是--(JAL)/-α(3.7)，4名是--(JAL)/α(Hph I)α，3名是--(JAL)/αα。他们复合杂合子的临床表现与中度Hb H病相符。在患者2（--(LOD)/-α(3.7)）中，尽管有7个已知基因、3个非编码RNA（ncRNA）、4个未知基因和2个假基因的杂合缺失，但没有出现其他症状。对更多α-thal缺失患者的进一步分析将对遗传咨询和适当治疗产生影响。
