ANK1和SPTB基因突变致遗传性球形红细胞增多症的临床特点及遗传学分析

该研究对5例遗传性球形红细胞增多症（HS）患儿的临床特点及ANK1和SPTB基因突变特征进行分析。5例患儿均通过外周血基因检测确诊。5例患儿均表现为贫血、黄疸、脾肿大。红细胞渗透脆性试验显示3例增高；Coombs试验、葡萄糖6磷酸脱氢酶测定、蔗糖溶血试验、酸化血清溶血试验、地中海贫血基因检测均为阴性；外周血涂片球形红细胞计数仅1例增加。高通量测序发现病例1~3存在ANK1基因突变，分别为c.3398（exon29）delA、c.4306C > T以及c.957（exon9）_c.961（exon9）delAATCT，其中c.3398（exon29）delA未见报道；病例4的SPTB基因存在C.318delGExon3突变；病例5存在SPTB基因合并SLC4A1基因突变，其中SPTB基因c.3484delC为自发突变，SLCA4A1基因的突变位点来自父亲，为非致病基因。该研究提示，贫血、黄疸、脾肿大是HS患儿主要的临床表现；多数HS患儿外周血球形红细胞计数无明显异常；基因检测有助于HS的精准诊断。

Clinical characteristics and genetic analysis of hereditary spherocytosis caused by mutations of ANK1 and SPTB genes

This study analyzed the clinical features of 5 children with hereditary spherocytosis (HS) and the characteristics of ANK1 and SPTB gene mutations. All 5 children were confirmed with HS by peripheral blood genetic detection. Anemia, jaundice and splenomegaly were observed in all 5 children. Three children had an increase in erythrocyte osmotic fragility. All 5 children had negative results of the Coombs test, glucose 6 phosphate dehydrogenase test, sucrose hemolysis test, acidified-serum hemolysis test and thalassemia gene test. Peripheral blood smear showed an increase in spherocyte count in one child. High-throughput sequencing revealed ANK1 gene mutations in patients 1 to 3, namely c.3398(exon29)delA, c.4306C > T and c.957(exon9)_c.961(exon9)delAATCT, among which c.3398(exon29)delA had not been reported before. Patient 4 had c.318delGExon3 mutation in the SPTB gene. Patient 5 had mutations in the SPTB and SLC4A1 genes, among which c.3484delC in the SPTB gene was a spontaneous mutation; the mutation site of the SLCA4A1 gene was inherited from the father and was a non-pathogenic gene. This study suggests that anemia, jaundice and splenomegaly are major clinical manifestations of HS children. Most children with HS do not have the typical spherocytic changes. Genetic detection may help with the accurate diagnosis of HS.