Giambona A, Lo Gioco P, Marino M, Abate I, Di Marzo R, Renda M, Di Trapani F, Messana F, Siciliano S, Rigano P
Servizio di Prevenzione e Cura della Talassemia, Unita' di Ricerca Piera Cutino, Ospedale V. Cervello, Palermo, Italy.
Hum Genet. 1995 May;95(5):526-30. doi: 10.1007/BF00223864.
This paper reports the results of 1428 beta-thalassemia chromosomes studied in Sicily during a hemoglobinopathy control program starting in 1983. Molecular screening was performed by direct restriction enzyme analysis, allele specific oligonucleotide (ASO) hybridization, reverse dot blot analysis (RDB) and, for the rare or new mutations, by direct sequencing of polymerase chain reaction (PCR) products. Using these approaches 1410 (98.7%) out of 1428 beta-globin gene defects were characterized, involving 22 different beta-thalassemia mutations. Three of these were present at high frequency (beta(0)39, IVS1, 110 and IVS1,6); the other beta-globin gene defects were found at lower frequency. In the latter, we found a smaller group of mutations at a frequency lower than 10% (IVS1, 1, IVS2, 745, beta S) and a larger one at a frequency lower than 2% [-87, IVS1,2, IVS2,1, fr 6, fr 8 (-AA), fr 44, fr 76, -101, IVS1, 116, IVS1, 3'end G-C, IVS1,5 G-A, IVS1,5 G-C, cod 30, Lepore, delta beta, beta C]. The possible origin of this very large number of mutations is discussed, taking into account the historical point of view. Moreover, this approach has made a first trimester prenatal diagnosis program possible in our region in practically all cases, with a great improvement in general thalassemia management.
本文报告了在1983年启动的血红蛋白病控制项目期间，在西西里岛对1428条β地中海贫血染色体进行研究的结果。通过直接限制性酶切分析、等位基因特异性寡核苷酸（ASO）杂交、反向斑点杂交分析（RDB）进行分子筛查，对于罕见或新的突变，则通过对聚合酶链反应（PCR）产物进行直接测序。使用这些方法，在1428个β珠蛋白基因缺陷中，有1410个（98.7%）得到了鉴定，涉及22种不同的β地中海贫血突变。其中三种突变高频出现（β(0)39、IVS1,110和IVS1,6）；其他β珠蛋白基因缺陷出现频率较低。在频率较低的后者中，我们发现一小部分突变频率低于10%（IVS1,1、IVS2,745、βS），还有一大部分突变频率低于2%[-87、IVS1,2、IVS2,1、fr 6、fr 8（-AA）、fr 44、fr 76、-101、IVS1,116、IVS1,3'端G-C、IVS1,5 G-A、IVS1,5 G-C、密码子30、Lepore、δβ、βC]。从历史角度考虑，讨论了如此大量突变的可能起源。此外，这种方法使我们地区几乎所有病例的孕早期产前诊断项目成为可能，大大改善了地中海贫血的总体管理。
