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Abstract：
OBJECTIVE: To understand the genotype and distribution of thalassemia in northern Guangxi.
METHODS: The study subjects were 55,281 individuals who came to the Affiliated Hospital of Guilin Medical University for genetic diagnosis of thalassemia from January 2012 to August 2023. All of their household registration was in the precincts of Guibei District and its affiliated counties. Red blood cell parameters and hemoglobin analysis were used for thalassemia screening. Gap-PCR, PCR-reverse dot blot hybridization (PCR-RDB), and multicolor melting curve analysis (MMCA) were used to identify common thalassemia genes. Multiplex ligation-dependent probe amplification (MLPA), Sanger sequencing, and third-generation single-molecule real-time (SMRT) sequencing were employed to identify rare thalassemia genes.
RESULTS: Among the 55,281 samples, 16,442 (29.74%) were diagnosed with thalassemia. The detection rates of α, β, and α combined β-thalassemia were 18.57%, 9.99% and 1.18%, respectively. Among ethnical groups, allele mutation frequency of thalassemia was the highest in Zhuang (44.97%), followed by Yao (40.11%), Dong (31.33%), Han (29.85%), Miao (24.31%), and Hui (20.6%). A total of 11,659 alleles (21.09%) of 8 types of α-thalassemia were identified in 55,281 samples, primarily --SEA (53.9%), followed by -α3.7 (21.3%), including rare alleles: --THAI (0.45%) and HKαα (0.38%). A total of 6367 (11.52%) and 14 types of β-thalassemia alleles were identified, mainly CD41-42 (50.12%), followed by CD17 (22.22%), including rare alleles: βCD37 (0.16%) and Gγ+ (Aγδβ)0/βN (0.05%). A total of 31 genotypes were detected in 10,264 cases of α-thalassemia, and the main types were --SEA/αα (53.23%), -α3.7/αα (19.15%), and -α4.2/αα (7.21%). A total of 34 genotypes were detected in 5525 cases of β-thalassemia, and the main types were βCD41-42/βN (50.53%), βCD17/βN (21.77%), and βIVS-II-654/βN (12.16%). A total of 78 gene types were detected in 653 cases of α- and β-thalassemia, and the main types were --SEA/αα, βCD41-42/βN (18.68%) and -α3.7/αα, βCD41-42/βN (13.02%). There were 580 cases (5.65%) of HbH disease (α0/α+), and 4 cases of Hemoglobin Bart\'s Hydrops Foetus syndrome (--SEA/--SEA). In addition, there were 92 cases (1.67%) of intermedia or severe types of β-thalassemia (β0/β0, β0/β+, β+/β+), including 23 cases of combined α-thalassemia. Among the samples screened negative for thalassemia, 3.7% of them were found to carry thalassemia genes, and 91.35% of the genotypes were αWSα/αα, -α3.7/αα, and -α4.2/αα. In addition, 40.26% of αWSα/αα, 22.89% of -α3.7/αα, and 18.51% of -α4.2/αα had no hematological phenotype.
CONCLUSIONS: The population in northern Guangxi exhibited rich ethnic diversity, with high allelic carrying rates among the Zhuang, Yao and Dong ethnic groups. Thalassemia gene mutations are diverse, encompassing a variety of gene types, with α thalassemia predominating, notably the --SEA/αα gene type. The prevalence of intermedia or severe types of thalassemia is not low, but there are still some carriers of thalassemia in people who are initially tested negative.
METHODS: The study subjects were 55,281 individuals who came to the Affiliated Hospital of Guilin Medical University for genetic diagnosis of thalassemia from January 2012 to August 2023. All of their household registration was in the precincts of Guibei District and its affiliated counties. Red blood cell parameters and hemoglobin analysis were used for thalassemia screening. Gap-PCR, PCR-reverse dot blot hybridization (PCR-RDB), and multicolor melting curve analysis (MMCA) were used to identify common thalassemia genes. Multiplex ligation-dependent probe amplification (MLPA), Sanger sequencing, and third-generation single-molecule real-time (SMRT) sequencing were employed to identify rare thalassemia genes.
RESULTS: Among the 55,281 samples, 16,442 (29.74%) were diagnosed with thalassemia. The detection rates of α, β, and α combined β-thalassemia were 18.57%, 9.99% and 1.18%, respectively. Among ethnical groups, allele mutation frequency of thalassemia was the highest in Zhuang (44.97%), followed by Yao (40.11%), Dong (31.33%), Han (29.85%), Miao (24.31%), and Hui (20.6%). A total of 11,659 alleles (21.09%) of 8 types of α-thalassemia were identified in 55,281 samples, primarily --SEA (53.9%), followed by -α3.7 (21.3%), including rare alleles: --THAI (0.45%) and HKαα (0.38%). A total of 6367 (11.52%) and 14 types of β-thalassemia alleles were identified, mainly CD41-42 (50.12%), followed by CD17 (22.22%), including rare alleles: βCD37 (0.16%) and Gγ+ (Aγδβ)0/βN (0.05%). A total of 31 genotypes were detected in 10,264 cases of α-thalassemia, and the main types were --SEA/αα (53.23%), -α3.7/αα (19.15%), and -α4.2/αα (7.21%). A total of 34 genotypes were detected in 5525 cases of β-thalassemia, and the main types were βCD41-42/βN (50.53%), βCD17/βN (21.77%), and βIVS-II-654/βN (12.16%). A total of 78 gene types were detected in 653 cases of α- and β-thalassemia, and the main types were --SEA/αα, βCD41-42/βN (18.68%) and -α3.7/αα, βCD41-42/βN (13.02%). There were 580 cases (5.65%) of HbH disease (α0/α+), and 4 cases of Hemoglobin Bart\'s Hydrops Foetus syndrome (--SEA/--SEA). In addition, there were 92 cases (1.67%) of intermedia or severe types of β-thalassemia (β0/β0, β0/β+, β+/β+), including 23 cases of combined α-thalassemia. Among the samples screened negative for thalassemia, 3.7% of them were found to carry thalassemia genes, and 91.35% of the genotypes were αWSα/αα, -α3.7/αα, and -α4.2/αα. In addition, 40.26% of αWSα/αα, 22.89% of -α3.7/αα, and 18.51% of -α4.2/αα had no hematological phenotype.
CONCLUSIONS: The population in northern Guangxi exhibited rich ethnic diversity, with high allelic carrying rates among the Zhuang, Yao and Dong ethnic groups. Thalassemia gene mutations are diverse, encompassing a variety of gene types, with α thalassemia predominating, notably the --SEA/αα gene type. The prevalence of intermedia or severe types of thalassemia is not low, but there are still some carriers of thalassemia in people who are initially tested negative.
摘要：
目的：了解广西北部地区地中海贫血的基因型及分布情况。
方法：研究对象为2012年1月至2023年8月到桂林医科大学附属医院进行地中海贫血基因诊断的55,281例。他们的所有户籍都在桂北区及其所属县的辖区内。红细胞参数和血红蛋白分析用于地中海贫血筛查。Gap-PCR,PCR-反向斑点杂交（PCR-RDB），和多色熔解曲线分析（MMCA）用于鉴定常见的地中海贫血基因。多重连接依赖性探针扩增(MLPA),桑格测序,和第三代单分子实时（SMRT）测序用于鉴定罕见的地中海贫血基因。
结果：在55,281个样本中，16,442（29.74％）被诊断为地中海贫血。α的检出率,β,α合并β-地中海贫血占18.57%,9.99%和1.18%，分别。在种族群体中，地中海贫血等位基因突变频率最高(44.97%),其次是姚明(40.11%)，董（31.33%），韩（29.85%），苗族(24.31%),和回族（20.6%）。在55,281份样本中共鉴定出8种α-地中海贫血的11,659个等位基因(21.09%),主要是--SEA（53.9%），其次是-α3.7（21.3%），包括稀有等位基因：-THAI（0.45％）和HKα（0.38％）。共鉴定出6367个(11.52%)和14种β-地中海贫血等位基因,主要是CD41-42（50.12%），其次是CD17（22.22%），包括罕见等位基因:βCD37(0.16%)和Gγ+(Aγδβ)0/βN(0.05%)。在10264例α-地中海贫血中共检测到31个基因型,主要类型为--SEA/αα(53.23%)，-α3.7/αα（19.15%），和-α4.2/αα(7.21%)。5525例β-地中海贫血患者共检测到34种基因型,主要类型为βCD41-42/βN（50.53%），βCD17/βN（21.77%），和βIVS-II-654/βN（12.16%）。在653例α-和β-地中海贫血中共检测到78个基因型,主要类型为--SEA/αα，βCD41-42/βN（18.68%）和-α3.7/αα，βCD41-42/βN（13.02%）。HbH病(α0/α+)580例(5.65%),血红蛋白巴特水肿胎儿综合征(--SEA/--SEA)4例。此外,中间型或重症型β地中海贫血92例(1.67%)(β0/β0,β0/β+,β+/β+)，其中合并α-地中海贫血23例。在地中海贫血筛查阴性的样本中，其中3.7%被发现携带地中海贫血基因，91.35%的基因型为αWSα/αα，-α3.7/αα,和-α4.2/αα。此外,αWSα/αα的40.26%,-α3.7/αα的22.89%，18.51%的-α4.2/αα无血液学表型。
结论：桂北地区人口呈现出丰富的民族多样性，壮族等位基因携带率高，瑶族和侗族。地中海贫血基因突变多样，包括多种基因类型，以α地中海贫血为主，特别是--SEA/αα基因型。中间型或严重型地中海贫血的患病率并不低，但是最初检测为阴性的人中仍然有一些地中海贫血的携带者。
方法：研究对象为2012年1月至2023年8月到桂林医科大学附属医院进行地中海贫血基因诊断的55,281例。他们的所有户籍都在桂北区及其所属县的辖区内。红细胞参数和血红蛋白分析用于地中海贫血筛查。Gap-PCR,PCR-反向斑点杂交（PCR-RDB），和多色熔解曲线分析（MMCA）用于鉴定常见的地中海贫血基因。多重连接依赖性探针扩增(MLPA),桑格测序,和第三代单分子实时（SMRT）测序用于鉴定罕见的地中海贫血基因。
结果：在55,281个样本中，16,442（29.74％）被诊断为地中海贫血。α的检出率,β,α合并β-地中海贫血占18.57%,9.99%和1.18%，分别。在种族群体中，地中海贫血等位基因突变频率最高(44.97%),其次是姚明(40.11%)，董（31.33%），韩（29.85%），苗族(24.31%),和回族（20.6%）。在55,281份样本中共鉴定出8种α-地中海贫血的11,659个等位基因(21.09%),主要是--SEA（53.9%），其次是-α3.7（21.3%），包括稀有等位基因：-THAI（0.45％）和HKα（0.38％）。共鉴定出6367个(11.52%)和14种β-地中海贫血等位基因,主要是CD41-42（50.12%），其次是CD17（22.22%），包括罕见等位基因:βCD37(0.16%)和Gγ+(Aγδβ)0/βN(0.05%)。在10264例α-地中海贫血中共检测到31个基因型,主要类型为--SEA/αα(53.23%)，-α3.7/αα（19.15%），和-α4.2/αα(7.21%)。5525例β-地中海贫血患者共检测到34种基因型,主要类型为βCD41-42/βN（50.53%），βCD17/βN（21.77%），和βIVS-II-654/βN（12.16%）。在653例α-和β-地中海贫血中共检测到78个基因型,主要类型为--SEA/αα，βCD41-42/βN（18.68%）和-α3.7/αα，βCD41-42/βN（13.02%）。HbH病(α0/α+)580例(5.65%),血红蛋白巴特水肿胎儿综合征(--SEA/--SEA)4例。此外,中间型或重症型β地中海贫血92例(1.67%)(β0/β0,β0/β+,β+/β+)，其中合并α-地中海贫血23例。在地中海贫血筛查阴性的样本中，其中3.7%被发现携带地中海贫血基因，91.35%的基因型为αWSα/αα，-α3.7/αα,和-α4.2/αα。此外,αWSα/αα的40.26%,-α3.7/αα的22.89%，18.51%的-α4.2/αα无血液学表型。
结论：桂北地区人口呈现出丰富的民族多样性，壮族等位基因携带率高，瑶族和侗族。地中海贫血基因突变多样，包括多种基因类型，以α地中海贫血为主，特别是--SEA/αα基因型。中间型或严重型地中海贫血的患病率并不低，但是最初检测为阴性的人中仍然有一些地中海贫血的携带者。
