桂北地区166例HbH病患儿血液学参数和基因谱分析

Hematologic parameters and genotype analysis in 166 children with HbH disease in the North Guangxi region

摘要:

目的：研究桂北地区HbH病患儿的基因谱特点及不同基因型HbH病的血液学参数特点。方法：根据临床表现、血细胞学检测、血红蛋白电泳确诊HbH病患儿166例，均来自桂北地区。Multi-PCR和PCR-反向斑点杂交确定基因型，对于经常规基因检测不能确诊的基因突变，采用直接DNA测序法。结果：166例确诊为HbH病的患儿中，共检出8种基因型，其中 --SEA/-α3.7 82例，--SEA/-α4.2 40例，--SEA/αCSα 38例，--SEA/αQSα 1例，--SEA/αWSα 1例，--SEA/αCD43/44（-C）α 1例，--SEA/-α3.7 复合CD17 （A→T）1例，--SEA/-α4.2 复合CD41-42（-TTCT）1例，另有1例为 --SEA与未知基因突变的双重杂合子。实际可分析血液学参数的HbH病患儿有134例，其中2例Hb在正常范围，36例轻度贫血，90例中度贫血，6例 --SEA/αCSα因合并感染而呈重度贫血；69例 --SEA/-α3.7患儿Hb为 62~120 g/L，31例 --SEA/-α4.2患儿Hb为 69~127 g/L，34例 --SEA/αCSα患儿Hb 为34~110 g/L。非缺失型HbH病组（基因型 --SEA/αCSα）Hb低于缺失型HbH病组（基因型 --SEA/-α 3.7和 --SEA/-α4.2）（P＜0.05），MCV含量高于缺失型HbH病组（P＜0.05）。结论：桂北地区HbH病患儿基因谱丰富，以缺失型HbH病为主，并有明显的遗传异质性；非缺失型HbH病患儿的贫血程度较缺失型HbH病组重，但MCV值较缺失型HbH病组高。

Abstract:

OBJECTIVE: To study the characteristics of genotype spectrum and hematologic parameters in children with HbH disease in the North Guangxi region. METHODS: HbH disease was identified by clinical manifestations, routine blood tests and hemoglobin electrophoresis in 166 children who came form the North Guangxi region. Genotypes were determined by Multi-PCR combined with PCR reverse dot blot. DNA sequencing was used when the genotype could not be identified by regular methods. RESULTS: Of the 166 children with HbH disease, 8 genotypes were identified: --SEA/-α3.7 (82 cases), --SEA/-α4.2 (40 cases), --SEA/αCSα (38 cases), --SEA/αQSα (1 case), --SEA/αWSα (1 case), --SEA/αCD43/44 (-C) α (1 case), --SEA/-α3.7 plus CD17 (A→T) (1 case) and --SEA/-α4.2 plus CD41-42(-TTCT) (1 case). One case was confirmed as the heterozygote of --SEA and an unknown mutation. In the 134 cases with complete medical data, 2 had normal hemoglobin levels, 36 manifested mild anemia, 90 manifested moderate anemia, and 6 (genotype: --SEA/αCSα) showed severe anemia because of the coexistence of infection. Children with the genotype of --SEA/-α3.7 (69 cases), --SEA/-α4.2 (31 cases) and --SEA/αCSα (34 cases) had hemoglobin levels of 62-120, 69-127 and 34-110 g/L respectively. The hemoglobin level in the --SEA/αCSα group was significantly lower than in the deletional HbH disease group (genotypes: --SEA/-α3.7 and --SEA/-α4.2 ) (P<0.05). In contrast, MCV levels in the --SEA/αCSα group were significantly higher than in the deletional HbH disease group (P<0.05). CONCLUSIONS: The genotype spectrum of HbH disease is diverse in the North Guangxi region. Deletional genotype is prevalent. The disease is heterogeneous. The children with --SEA/αCSα HbH disease have severer anemia and higher MCV levels than those with deletional HbH disease.