Identification of a Novel Mutation of β-Spectrin in Hereditary Spherocytosis Using Whole Exome Sequencing

• Published in: International journal of molecular sciences Vol. 22; no. 20; p. 11007
• Main Authors: Bogusławska, Dżamila M, Skulski, Michał, Machnicka, Beata, Potoczek, Stanisław, Kraszewski, Sebastian, Kuliczkowski, Kazimierz, Sikorski, Aleksander F
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 12.10.2021; MDPI
• Subjects: actin binding domain; Adult; Anemia; Blood; Case Report; Congenital diseases; Erythrocytes; Female; Genes; Genetic engineering; Genomes; Genotype & phenotype; Hemolytic anemia; Hereditary diseases; Hereditary spherocytosis; Humans; Kinases; Middle Aged; Missense mutation; Mutation; Mutation, Missense; Population; Proteins; Signs and symptoms; Spectrin; Spectrin - chemistry; Spectrin - genetics; Spherocytosis; Spherocytosis, Hereditary - diagnosis; Spherocytosis, Hereditary - genetics; sptb gene; Structure-function relationships; Whole Exome Sequencing; β-spectrin; actin binding domain; hereditary spherocytosis; β-spectrin; whole exome sequencing
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms222011007

Hereditary spherocytosis (HS), the most commonly inherited hemolytic anemia in northern Europeans, comprises a group of diseases whose heterogeneous genetic basis results in a variable clinical presentation. High-throughput genome sequencing methods have made a leading contribution to the recent progress in research on and diagnostics of inherited diseases and inspired us to apply whole exome sequencing (WES) to identify potential mutations in HS. The data presented here reveal a novel mutation probably responsible for HS in a single Polish family. Patients with clinical evidence of HS (clinical symptoms, hematological data, and EMA test) were enrolled in the study. The examination of the resulting WES data showed a number of polymorphisms in 71 genes associated with known erythrocyte pathologies (including membranopathies, enzymopathies, and hemoglobinopathies). Only a single gene variant indicated the possible molecular mechanism of the disease in the studied family. The new missense mutation p.C183Y was identified using WES in the gene, which is most likely the cause of clinical symptoms typical of hereditary spherocytosis (membranopathy) due to structural and functional impairments of human β-spectrin. This mutation allows for a better understanding of the molecular mechanism(s) of one of the membranopathies, hereditary spherocytosis.