Two novel spontaneous ANK1 frameshift mutation and splicing mutation in two Chinese families with Hereditary spherocytosis. Search for disease-causing gene mutations and predict their pathogenicity

Background Hereditary spherocytosis (HS), inherited by an autosomal dominant manner, is a common clinical heterogeneous disease characterized by a large number of irregularly shaped red blood cells (primarily spherical) in the blood, and can lead to chronic hemolytic anaemia. So far, several pathogenic genes related to HS have been identified, including SPTA1, SPTB, SLC4A1, EPB42 and ANK1. In this study, we discussed two de novo ANK1 mutations and the relationship between genotype and phenotype in the Chinese Han families with HS. Methods DNA was extracted from the peripheral blood of the two patients and their families and healthy individuals. Whole-exome sequencing (WES) together with Sanger sequencing was performed on genomic DNA to verify the mutations identified in their families. Results Two novel ANK1 mutations were identified in two patients from unrelated families, c.4136dupC (p. T1380Dfs * 12) in family A and c.4391-1G> C in family B. Then we performed Sanger sequencing analysis on the samples of two probands and their parents, indicating that the two mutations were spontaneous. Conclusion Our results showed that two novel mutations in ANK1 may lead to the occurrence of HS. These findings provide new information to clarify the genotype-phenotype association of HS and enrich the pathogenic variation spectrum of ANK1, so as to make a more accurate prenatal diagnosis and timely treatment of HS.