Chang Jan-Gowth, Tsai Wen-Chan, Chong Inn-Wen, Chang Chao-Sung, Lin Chyi-Chang, Liu Ta-Chih
Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Haematologica. 2008 Jun;93(6):913-6. doi: 10.3324/haematol.12195. Epub 2008 Apr 15.
beta-thalassemia major can be caused by homozygosity or compound heterozygosity for beta-globin gene mutations (HBB gene). Most cases are inherited from parents who both have diseased alleles of the HBB gene. We report a patient with late-onset beta-thalassemia major that evolved from beta-thalassemia minor in which only one of her parents had the diseased HBB gene. To study the cause of beta-thalassemia major in this patient, we performed the 100K single nucleotide polymorphism genotyping assay, fluorescence in situ hybridization, and DNA methylation analysis of the imprinting genes near the HBB gene. The results showed a loss of heterozygosity in the region of chromosome 11p14.3 to 11p15.5, which perfectly matched one allele of her father. Our study demonstrates that paternal uniparental isodisomy of chromosomal 11p15.5 is associated with the beta-thalassemia major in this patient. Key words: beta-thalassemia major, uniparental isodisomy, mosaicism.
重型β地中海贫血可由β珠蛋白基因突变(HBB基因)的纯合性或复合杂合性引起。大多数病例是从父母双方都有HBB基因致病等位基因遗传而来。我们报告了一名迟发性重型β地中海贫血患者,其由轻型β地中海贫血发展而来,而她的父母中只有一方有致病的HBB基因。为了研究该患者重型β地中海贫血的病因,我们进行了100K单核苷酸多态性基因分型检测、荧光原位杂交以及HBB基因附近印记基因的DNA甲基化分析。结果显示,11号染色体p14.3至p15.5区域出现杂合性缺失,这与她父亲的一个等位基因完全匹配。我们的研究表明,11号染色体p15.5的父源单亲二体性与该患者的重型β地中海贫血有关。关键词:重型β地中海贫血;单亲二体性;嵌合体