Efremov G D
Macedonian Academy of Sciences and Arts, National Reference Laboratory for Hemoglobinopathies, Skopje, Republic of Macedonia, Yugoslavia.
Hemoglobin. 1992;16(6):531-44. doi: 10.3109/03630269208993124.
This paper summarizes information on the epidemiology and molecular basis of hemoglobinopathies in Yugoslavia. Over the past 25 years, population surveys of more than 28,000 school children from all over the country, except Slovenia, have shown that the average incidence of beta-thalassemia (beta-thal) trait is 1.2%, ranging from 2.9% in the south (Macedonia) to 0.8% in the northwest (Croatia). The frequency of delta beta-thal is 0.2%, while the frequency of the Swiss type of hereditary persistence of fetal hemoglobin (HPFH) is 0.4%. Screening of 6,400 newborns has shown that the frequency of alpha-thal trait is 1.6%. The molecular basis of the different forms of beta-thal among Yugoslavians has been almost completely defined. Over 250 beta-thal chromosomes have been studied, and in over 90% the molecular defect was determined. Eighteen different beta-thal mutations have been detected, three of which (IVS-I-110, G-->A; IVS-I-6, T-->C; IVS-I-1, G-->A) account for more than 70% of all beta-thal chromosomes. Four new mutations [-87 (C-->A); IVS-II-850 (G-->C); initiation codon mutation T-->C; poly A (AATAAA-->AATGAA)] and one new deletion (1605 bp) have been characterized. Molecular analyses of DNA from over 30 unrelated cases with delta beta-thal have shown that this condition is mainly caused by a 13 kb deletion (Sicilian type); in one family a deletion of > 18 to 23 kb (Macedonian type), and in another family a deletion of 148 kb (Yugoslavian type of epsilon gamma delta beta-thal) of the globin gene complex was discovered. Limited studies of alpha-thal in Yugoslavia have shown the following types of molecular defects: approximately 20.5 kb deletion, approximately 17.5 kb deletion, -3.7 kb deletion, 5 nucleotide (nt) deletion, and Hb Icaria. The incidence of abnormal hemoglobins (Hbs) in Yugoslavia is 0.3%. Five different alpha chain variants among 21 families, 15 different beta chain variants among 53 families, one delta chain variant in one family, one variant with a deleted residue in one family, and two types of Hb Lepore among 122 families, have been observed.
本文总结了南斯拉夫血红蛋白病的流行病学和分子基础方面的信息。在过去25年里，对除斯洛文尼亚外来自全国各地的28000多名学童进行的人口调查显示，β地中海贫血（β-地贫）特征的平均发病率为1.2%，范围从南部（马其顿）的2.9%到西北部（克罗地亚）的0.8%。δβ-地贫的频率为0.2%，而瑞士型胎儿血红蛋白遗传性持续存在（HPFH）的频率为0.4%。对6400名新生儿的筛查显示，α-地贫特征的频率为1.6%。南斯拉夫人中不同形式β-地贫的分子基础几乎已完全明确。已研究了250多条β-地贫染色体，其中90%以上的分子缺陷已确定。已检测到18种不同的β-地贫突变，其中三种（IVS-I-110，G→A；IVS-I-6，T→C；IVS-I-1，G→A）占所有β-地贫染色体的70%以上。已鉴定出四种新突变[-87（C→A）；IVS-II-850（G→C）；起始密码子突变T→C；多聚A（AATAAA→AATGAA）]和一种新的缺失（1605 bp）。对30多例无关的δβ-地贫病例的DNA进行分子分析表明，这种情况主要由13 kb的缺失（西西里型）引起；在一个家族中发现了大于18至23 kb的缺失（马其顿型），在另一个家族中发现了珠蛋白基因复合体148 kb的缺失（南斯拉夫型εγδβ-地贫）。在南斯拉夫对α-地贫进行的有限研究显示了以下几种分子缺陷类型：约20.5 kb的缺失、约17.5 kb的缺失、-3.7 kb的缺失、5个核苷酸（nt）的缺失以及血红蛋白伊卡里亚。南斯拉夫异常血红蛋白（Hb）的发病率为0.3%。在21个家族中观察到5种不同的α链变体，在53个家族中观察到15种不同的β链变体，在1个家族中观察到1种δ链变体，在1个家族中观察到1种带有缺失残基的变体，在122个家族中观察到2种类型的血红蛋白 Lepore。
