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

Abstract

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.