Supplementary Material for: A novel ANK1 mutation in a neonatal hereditary spherocytosis case: Diagnostic challenges and familial genetic analysis

Hereditary spherocytosis (HS) is a congenital disease in which erythrocyte membranes are abnormal, with ANK1 defects as the main cause. The diagnosis of neonatal HS is difficult due to poor phenotypic specificity. Therefore, a detailed inquiry into family history may be helpful for diagnosis. Here, we describe a familial case of HS caused by a novel mutation in ANK1. The proband is a premature infant of Chinese Han ethnicity, characterized by progressive aggravation of anemia and jaundice. The disease was caused by a frameshift mutation (c.3392delT/p.Leu1131Argfs*15) of ANK1 that was identified by genetic testing. In vitro functional experiments showed that this variant may seriously affect the protein expression, and further expanded the mutation spectrum of ANK1-HS. In this case, we emphasize the diagnostic value of early-intervention genetic testing for neonatal hemolytic anemia with a family history.

遗传性球形红细胞增多症（Hereditary spherocytosis, HS）是一类以红细胞膜结构异常为特征的先天性疾病，其中锚蛋白1（ANK1）基因缺陷为最主要的致病原因。因表型特异性不足，新生儿HS的诊断难度较大，详细追溯家族史或可辅助临床诊断。本文报道1例由ANK1基因新发突变引发的家族性HS病例：先证者为中国汉族早产儿，临床以贫血与黄疸进行性加重为主要表现；经基因检测确认，其致病突变类型为ANK1基因移码突变（c.3392delT/p.Leu1131Argfs*15）。体外功能实验证实，该变异可显著影响蛋白质表达，进一步拓展了ANK1相关HS的突变谱。本案例凸显了早期干预性基因检测对伴家族史新生儿溶血性贫血的诊断价值。