Two Variants of the ANK1 Gene Associated with Hereditary Spherocytosis

<b>Background</b> Hereditary spherocytosis (HS) is an erythrocytic membranopathy that belongs to a group of rare genetic disorders. Mutations in five genes, including <i>ANK1</i>, cause clinical manifestations of the disease. Identified variations in individual families provide a better understanding of the molecular basis of the disease. <b>Methods</b> In this study, we used two sequencing methods, whole exome sequencing (WES) and Sanger sequencing, analyzing gDNA and cDNA as templates, to detect and verify the variants putatively responsible for the clinical symptoms observed in a Polish family diagnosed with HS. <b>Results</b> We detected two variants that occur in <i>cis</i> in the <i>ANK1</i> gene, a known missense mutation (NP_000028.3:p.V463I) and a novel frameshift mutation (NP_000028.3: p.V1626fs*64) that appears to be crucial for the probands. As shown by transcriptome studies, the mutant allele is not present at a detectable level. <b>Conclusions</b> We conclude that the molecular basis of this case is related to an unstable transcript of the mutant allele and that the direct cause of the HS is a deficiency of erythrocyte ankyrin leading to a disruption of the AE1-erythrocyte ankyrin-spectrin complex in the erythrocyte membrane.