[Analysis of the Types of Thalassemia Gene Mutations in Nanping Area of Fujian, China].

To investigation the types and frequencies of thalassemia gene mutations in pregnant population in Nanping area of Fujian Province, so as to provide a basis for prevention and control of birth children with moderate and severe thalassaemia in this area.The genotyping of α and β thalassemia was performed using the gap-PCR (gap-PCR) technique combined with reverse dot blot (RDB). The genotyping test was performed by Gap-PCR for three rare deficient thalassemia. The cases with negative detection were further detected by Sanger sequencing method, so as to identify rare α or β thalassemia mutation.1120 specimens were genotyped for thalassemia, out of them 547 thalassemia genes were determined. The detection rate was 48.8% (547/1120). 340 specimens were diagnosed as α thalassemia, and the detection rate was 30.6%, including 266 cases of --SEA/αα, 44 cases of -α3.7/αα, 12 cases of -α4.2/αα, 8 cases of ααQS/αα,. 3 cases of Hb H disease ( 2 cases of --SEA/-α3.7, 1 case of --SEA/-α4.2), 2 cases of ααCS/αα, 2 cases of ααWS/αα, 1 case of -α3.7/-α3.7, and 1 case of -α3.7/ααQS. Also, they contain 11 cases of rare α thalassemia, 8 kinds of rare types of α thalassemia mutations in combination, such as 4 cases of ααIVS-II-55 (T→G) in α1/αα, 1 case of ααIVS-I-62 (C→T) in α1/αα, 1 case of ααCD106（CTG→GTG）in α2/αα, 1 case of ααHBA2:c.-24C>G/αα, 1 case of ααIVS-II-55 (T→G) in α1/ααIVS-II-55 (T→G) in α1, 1 case of ααIVS-II-55 (T→G) in α1/ααIVS-II-119 (G;+CTCGGCCC) in α2, 1 case of ααIVS-II-88 (G→A) in α2/αα, and 1 case of --THAI/αα. Among them, 5 α mutation sites were first reported, namely ααIVS-I-62 (C→T) in α1, ααIVS-II-55 (T→G) in α1, ααIVS-II-119 (G; +CTCGGCCC ) in α2, ααIVS-II-88 (G→A) in α2 and ααCD106 (CTG→GTG) in α2; 2 α thalassemia mutation sites: ααHBA2: c.-24C>G and --THAI were detected again in the Chinese population, respectively. 188 specimens were diagnosed as β thalassemia with a detection rate of 16.8%. Among them, 68 cases of βIVS-II-654/βN, 47 cases of βCD41-42/βN, 20 cases of βCD17/βN, 17 cases of β-28/βN, 7 cases of βCD27-28/βN, 7 cases of βE/βN, 3 cases of βCD71-72/βN and 2 cases of βCD43/βN. And 17 cases were diagnosed as rare β thalassemia, 8 kinds of rare types were β thalassemia mutations in combination. There were 4 cases of βIVS-II-81 (C→T)/βN, 3 cases of βHb J-Bangkok/βN, 3 cases of βHb New York/βN, 2 cases of β-96 (G→T)/βN, 2 cases of βIVS-II-806 (G→C)/βN, 1 case of βCodons 8/9/βN, 1 case of βHb G-Coushatta/βN, 1 case of βIVS-II-827 (A→T)/βN. Among them, 3 β thalassemia mutation sites were reported for the first time, namely β-96 (G→T), βIVS-II-806 (G→C) and βIVS-II-827 (A→T); it was found that in the Chinese population as βCodons 8/9, βHb G-Coushatta, βHb J-Bangkok, βHb New York, and βIVS-II-81 (C→T), respectively. 19 cases were diagnosed as αβ-complex thalassemia, out of which 15 types of thalassemia mutation combinations were detected. They contain 2 cases of rare αβ-complex thalassemia, which are ααIVS-II-55 (T→G)/αα complex βIVS-II-81 (C→T)/βN, ααIVS-II-65 (G→A) in α1/αα complex βHb G-Coushatta/βN.The types of thalassemia gene mutations in Nanping area of Fujian province are genetically heterogeneous. The prevention and control strategies of thalassaemia in this area should be based on the prevention and treatment of common α thalassemia and β thalassaemia. And the attention should be paid to the types of rare and unknown gene mutations using screening and testing method.中国福建南平地区地中海贫血基因突变类型研究.了解福建省南平地区地中海贫血基因突变类型及频率，为本地区预防和控制中型和重型地中海贫血患儿的出生提供依据，减少出生缺陷.采用跨越断裂点PCR（gap-PCR）技术结合反向点杂交法（RDB）进行α和β地中海贫血基因分型检测，对基因分型检测阴性者应用Gap-PCR法进行3种罕见缺失型地中海贫血检测，对检测阴性者采用Sanger测序法进行罕见α地中海贫血突变和β地中海贫血突变检测.1 120例标本参加地中海贫血基因分型检测，检出547例地中海贫血基因，检出率为48.8%（547/1120）。340例标本确诊为α地中海贫血，检出率为30.6%，其中--SEA/αα 256例、-α3.7/αα 44例、-α4.2/αα 12例、ααQS/αα 8例、Hb H病3例（--SEA/-α3.7 2例，--SEA/-α4.2 1例）、ααCS/αα 2例、ααWS/αα 2例、-α3.7/-α3.7 1例、-α3.7/ααQS 1例。1 120例中含有11例罕见型α地中海贫血，8种罕见α地中海贫血突变组合类型，分别是ααIVS-II-55 (T→G) in α1/ αα 4例、ααIVS-I-62(C→T) in α1/αα 1例、ααCD106（CTG→GTG）in α2/αα 1例、ααHBA2: c.-24C>G/αα 1例、ααIVS-II-55(T→G) in α1/ ααIVS-II-55(T→G) in α11例、ααIVS-II-55(T→G) in α1/ααIVS-II-119(G; +CTCGGCCC) in α2 1例、ααIVS-II-88(G→A) in α2/αα 1例和--THAI/αα 1例。其中，5种α突变位点是首次报道，分别是ααIVS-I-62(C→T) in α1、ααIVS-II-55(T→G) in α1、ααIVS-II-119(G; +CTCGGCCC) in α2、ααIVS-II-88(G→A) in α2和ααCD106（CTG→GTG）in α2；2种α突变位点再次在中国人群中检测到，分别是ααHBA2:c.-24C>G和--THAI。188例标本确诊为β地中海贫血，检出率为16.8%，其中βIVS-II-654/βN 68例、βCD41-42/βN 47例、βCD17/βN 20例、β-28/βN 17例，βCD27-28/βN 7例、βE/βN 7例、βCD71-72/βN 3例、βCD43/βN 2例。同时，含有17例罕见型β地中海贫血，8种罕见β地中海贫血突变组合类型，分别是βIVS-II-81(C→T)/βN 4例、βHb J-Bangkok/βN 3例，βHb New York/βN 3例、β-96(G→T)/βN 2例、βIVS-II-806(G→C)/βN 2例、βCodons 8/9/βN 1例、βHb G-Coushatta/βN 1例、βIVS-II-827(A→T)/βN 1例。其中有3个β突变位点是首次报道，分别是β-96(G→T)、βIVS-II-806(G→C)和βIVS-II-827(A→T)；β突变位点再次在中国人群中检测到，分别是βCodons 8/9、βHb G-Coushatta、βHb J-Bangkok、βHb New York和βIVS-II-81(C→T)。19例确诊α地中海贫血复合β地中海贫血，共检出15种地中海贫血突变组合类型，包含2例罕见稀有α地中海贫血复合β地中海贫血，分别是ααIVS-II-55(T→G)/αα复合βIVS-II-81(C→T)/βN、ααIVS-II-65(G→A)in α1/αα复合βHb G-Coushatta/βN.福建省南平地区地中海贫血基因突变类型具有遗传异质性，本地区地中海贫血防治策略应该以常见α-地中海贫血和β-地中海贫血的防治干预为主，同时也要重视罕见和未知基因突变类型的筛查和检测.