title: Mutational characteristics of ANK1 and SPTB genes in hereditary spherocytosis.
abstract: The aim of this study was to describe the mutational characteristics in Korean hereditary spherocytosis (HS) patients. Relevant literatures including genetically confirmed cases with well-documented clinical summaries and relevant information were also reviewed to investigate the mutational gene- or domain-specific laboratory and clinical association. Twenty-five HS patients carried one heterozygous mutation of ANK1 (n = 13) or SPTB (n = 12) but not in SPTA1, SLC4A1, or EPB42. Deleterious mutations including frameshift, nonsense, and splice site mutations were identified in 91% (21/23), and non-hotspot mutations were dispersed across multiple exons. Genotype-phenotype correlation was clarified after combined analysis of the cases and the literature review; anemia was most severe in HS patients with mutations on the ANK1 spectrin-binding domain (p < 0.05), and SPTB mutations in HS patients spared the tetramerization domain in which mutations of hereditary elliptocytosis and pyropoikilocytosis are located. Splenectomy (17/75) was more frequent in ANK1 mutant HS (32%) than in HS with SPTB mutation (10%) (p = 0.028). Aplastic crisis occurred in 32.0% of the patients (8/25; 3 ANK1 and 5 SPTB), and parvovirus B19 was detected in 88%. The study clarifies ANK1 or SPTB mutational characteristics in HS Korean patients. The genetic association of laboratory and clinical aspects suggests comprehensive considerations for genetic-based management of HS.
authors.affiliation: Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.|Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: J
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.|The Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: D-C
authors.initials: DC
authors.lastname: Jeong
authors.affiliation: Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.|Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: J
authors.initials: J
authors.lastname: Yoo
authors.affiliation: Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.|Division of Laboratory Medicine, Samkwang Medical Laboratories, Seoul, Republic of Korea.
authors.forename: W
authors.initials: W
authors.lastname: Jang
authors.affiliation: Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.|Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: H
authors.initials: H
authors.lastname: Chae
authors.affiliation: Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: J
authors.initials: J
authors.lastname: Kim
authors.affiliation: Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: A
authors.initials: A
authors.lastname: Kwon
authors.affiliation: Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: H
authors.initials: H
authors.lastname: Choi
authors.affiliation: Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: J W
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: N-G
authors.initials: NG
authors.lastname: Chung
authors.affiliation: Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.|Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: M
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.|Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Y
authors.initials: Y
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D017487:Ankyrins / Q000235:genetics*; D044466:Asian People; D002648:Child; D002675:Child, Preschool; D005091:Exons; D015870:Gene Expression; D056726:Genetic Association Studies; D055106:Genome-Wide Association Study; D006579:Heterozygote; D006801:Humans; D007223:Infant; D009154:Mutation; D010322:Parvoviridae Infections / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D016732:Parvovirus B19, Human / Q000302:isolation & purification; D012720:Severity of Illness Index; D013049:Spectrin / Q000235:genetics*; D013103:Spherocytosis, Hereditary / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D013156:Splenectomy
chemical_list: C110202:ANK1 protein, human; D017487:Ankyrins; C452439:SPTBN1 protein, human; D013049:Spectrin
keywords: ANK1; SPTB; genotype-phenotype correlation; hereditary spherocytosis; molecular analysis