Craig J E, Barnetson R A, Prior J, Raven J L, Thein S L
MRC Molecular Haematology Unit, John Radcliffe Hospital, Headington, Oxford, UK.
Blood. 1994 Mar 15;83(6):1673-82.
A considerable number of deletions of variable size and position that involve the beta-globin gene complex on chromosome 11 are associated with the clinical entities of hereditary persistence of fetal hemoglobin (HPFH) and delta beta thalassemia. Specific deletions appear to be associated with consistent phenotypes and some are known to be recurrent. To facilitate the molecular diagnosis of uncharacterized patients with HPFH and delta beta thalassemia, oligonucleotide primers have been designed to enzymatically amplify deletion-specific products for nine known deletions, which include those responsible for HPFH-1, HPFH-2, HPFH-3, Spanish (delta beta)zero thalassemia, hemoglobin (Hb) Lepore, Sicilian (delta beta)zero thalassemia, Chinese G gamma(A gamma delta beta)zero thalassemia, Asian-Indian inversion-deletion G gamma(A gamma delta beta)zero thalassemia, and Turkish inversion-deletion (delta beta)zero thalassemia. Using this approach, we have successfully characterized the molecular basis for delta beta thalassemia in 23 individuals from 16 families of diverse ethnic origins. Thirteen individuals from this group were shown to be heterozygous for the 13.4-kb Sicilian deletion, two were heterozygous for the 100-kb Chinese G gamma(A gamma delta beta)zero deletion, four were heterozygous for the Turkish form of inversion-deletion delta beta thalassemia, and three were heterozygous for the Asian-Indian form of inversion-deletion G gamma(A gamma delta beta)zero thalassemia. One Vietnamese subject was heterozygous for a 12.6-kb deletion, which we have fully characterized at the molecular level. Sequence analysis of the breakpoint regions of the Chinese deletion and the Turkish rearrangement indicates that, in each case, the mutation is likely to have arisen from a single origin. This hypothesis is supported by the evident geographical clustering of the various deletions described here.
相当数量的大小和位置可变的缺失涉及11号染色体上的β-珠蛋白基因复合体，这些缺失与胎儿血红蛋白遗传性持续存在（HPFH）和δβ地中海贫血的临床实体相关。特定的缺失似乎与一致的表型相关，并且已知一些是反复出现的。为了便于对未确诊的HPFH和δβ地中海贫血患者进行分子诊断，已设计了寡核苷酸引物，用于酶促扩增9种已知缺失的缺失特异性产物，其中包括导致HPFH-1、HPFH-2、HPFH-3、西班牙（δβ）0地中海贫血、血红蛋白（Hb）Lepore、西西里（δβ）0地中海贫血、中国Gγ（Aγδβ）0地中海贫血、亚洲-印度倒位-缺失Gγ（Aγδβ）0地中海贫血和土耳其倒位-缺失（δβ）0地中海贫血的缺失。使用这种方法，我们成功地确定了来自16个不同种族家庭的23名个体中δβ地中海贫血的分子基础。该组中的13名个体被证明是13.4 kb西西里缺失的杂合子，2名是100 kb中国Gγ（Aγδβ）0缺失的杂合子，4名是土耳其形式的倒位-缺失δβ地中海贫血的杂合子，3名是亚洲-印度形式的倒位-缺失Gγ（Aγδβ）0地中海贫血的杂合子。一名越南受试者是12.6 kb缺失的杂合子，我们已在分子水平上对其进行了全面表征。中国缺失和土耳其重排断点区域的序列分析表明，在每种情况下，突变可能都源于单一来源。这里描述的各种缺失明显的地理聚集支持了这一假设。
