Identification of a novel p.Q1772X ANK1 mutation in a Korean family with hereditary spherocytosis

• Published in: PloS one Vol. 10; no. 6; p. e0131251
• Main Authors: Han, Joo Hyung, Kim, Seung, Jang, Hoon, Kim, So Won, Lee, Min Goo, Koh, Hong, Lee, Ji Hyun
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 24.06.2015; Public Library of Science (PLoS)
• Subjects: Anemia; Ankyrins - genetics; Codon, Nonsense; Comorbidity; Consent; Disease; DNA Mutational Analysis; Etiology; Exome; Families & family life; Family Health; Female; Gallstones; Gene sequencing; Genes; Genetic aspects; Genetic screening; Genetic testing; Genomes; Genomics; Hematology; Hemolytic anemia; Hereditary spherocytosis; Heredity; Heterozygote; Hospitals; Humans; Hyperbilirubinemia - genetics; Male; Medicine; Middle Aged; Mutation; Nonsense mutation; Pediatrics; Pedigree; Pharmacology; Proteins; Republic of Korea; Spherocytosis; Spherocytosis, Hereditary - genetics; Splenectomy; Young Adult; Republic of Korea
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0131251

Hereditary spherocytosis (HS), a common form of inherited hemolytic anemia, is a heterogeneous group of disorders with regard to clinical severity, protein defects, and mode of inheritance. Causal mutations in at least five genes have been reported so far. Because multiple genes have been associated with HS, clinical genetic testing that relies on direct sequencing will be a challenge. In this study, we used whole exome sequencing to identify a novel nonsense mutation in ANK1 (p.Q1772X, NM_020476) that resulted in a truncated protein in a Korean patient with HS. Sanger sequencing confirmed the two affected individuals in the patient's family were heterozygous for the mutation. This is the first report of a Korean family that carries an ANK1 mutation responsible for HS. Our results demonstrate that next generation sequencing is a powerful approach for rapidly determining the genetic etiology of HS.