Hereditary stomatocytosis (HSt) is a type of congenital hemolytic anemia caused by abnormally increased cation permeability of erythrocyte membranes. Dehydrated HSt (DHSt) is the most common subtype of HSt and is diagnosed based on clinical and laboratory findings related to erythrocytes. PIEZO1 and KCNN4 have been recognized as causative genes, and many related variants have been reported. We analyzed the genomic background of 23 patients from 20 Japanese families suspected of having DHSt using a target capture sequence and identified pathogenic/likely pathogenic variants of PIEZO1 or KCNN4 in 12 families.
Hemolytic anemia: new variants in hereditary subtypes: Genetic variants identified in 12 Japanese families are likely to be responsible for a rare hereditary condition causing red blood cells (RBCs) to rupture. Keiko Shimojima Yamamoto of Tokyo Women’s Medical University, Japan, and colleagues conducted genetic analyses on blood samples from 23 people in 20 Japanese families with suspected dehydrated hereditary spherocytosis (DHSt), caused by RBC ion imbalances leading to dehydration and rupture. In 12 families, the analyses revealed probable disease-causing variants in two genes, PIEZO1 and KCNN4, some of which were identified for the first time. Both genes are related to RBC ion channels and the mutations lead to two slightly different forms of DHSt. Further understanding could improve treatment strategies. Comprehensive genomic analysis is a powerful tool for understanding the genetic cause of congenital hemolytic anemia.