title: Prevalence of type 5 familial hemophagocytic lymphohistiocytosis in Korea and novel mutations in STXBP2.
abstract: Familial hemophagocytic lymphohistiocytosis (F-HLH or FHL) is a potentially fatal immune dysregulation syndrome with a heterogeneous genetic background. Most recently, STXBP2 has been identified as the causative gene of type 5 FHL (FHL5) with a worldwide distribution. In this study, we investigated the prevalence of FHL5 in Korea. About 50 Korean pediatric patients with HLH who lacked pathogenic mutations in PRF1, UNC13D, or in STX11 from the previous series of 72 patients with HLH were analyzed for STXBP2 mutations by conventional sequencing analyses. As a result, we found one patient with two novel mutations of STXBP2: c.184A>G and c.577A>C. c.184A>G (p.Asn62Asp) was located within a highly conserved region of the STXBP2 protein and predicted to be deleterious. c.577A>C in exon 7 resulted in incomplete splicing mutation with exon 7 skipping concurrent with exon 7-retained transcript with p.Lys193Gln substitution. The frequency of FHL5 was ~1% (1/72) in Korean pediatric patients with HLH. This is the first study on FHL5 in Korea, and the data from a nationwide patient cohort provide another piece of genetic profiles of FHL.
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.|Department of Laboratory Medicine, Gachon University Gil Medical Center, Incheon, Korea.
authors.forename: J Y
authors.initials: JY
authors.lastname: Seo
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea.
authors.forename: K-O
authors.initials: KO
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: K-H
authors.initials: KH
authors.lastname: Yoo
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: K-W
authors.initials: KW
authors.lastname: Sung
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: H H
authors.initials: HH
authors.lastname: Koo
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: S-H
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: H J
authors.initials: HJ
authors.lastname: Kang
authors.affiliation: Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: K-D
authors.initials: KD
authors.lastname: Park
authors.affiliation: Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: H Y
authors.initials: HY
authors.lastname: Shin
authors.affiliation: Department of Pediatrics, Chonnam National University Hwasun Hospital, Chonnam, Korea.
authors.forename: H-J
authors.initials: HJ
authors.lastname: Baek
authors.affiliation: Department of Pediatrics, Chonnam National University Hwasun Hospital, Chonnam, Korea.
authors.forename: H
authors.initials: H
authors.lastname: Kook
authors.affiliation: Department of Pediatrics, Yonsei University Severance Hospital, Seoul, Korea.
authors.forename: C J
authors.initials: CJ
authors.lastname: Lyu
authors.affiliation: Department of Pediatrics, Kangdong Sacred Heart Hospital, University of Hallym College of Medicine, Seoul, Korea.
authors.forename: J-S
authors.initials: JS
authors.lastname: Song
authors.affiliation: Department of Pediatrics, Dankook University College of Medicine, Cheonan, Korea.
authors.forename: M J
authors.initials: MJ
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, Korea.
authors.forename: J-Y
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, Pusan National University Hospital, Pusan, Korea.
authors.forename: Y-T
authors.initials: YT
authors.lastname: Lim
authors.affiliation: Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: K-N
authors.initials: KN
authors.lastname: Koh
authors.affiliation: Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: H J
authors.initials: HJ
authors.lastname: Im
authors.affiliation: Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: J J
authors.initials: JJ
authors.lastname: Seo
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: H-J
authors.initials: HJ
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D051359:Lymphohistiocytosis, Hemophagocytic / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D051938:Munc18 Proteins / Q000737:chemistry / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D015995:Prevalence; D017434:Protein Structure, Tertiary; D012313:RNA / Q000235:genetics; D056910:Republic of Korea
chemical_list: D051938:Munc18 Proteins; C497940:STXBP2 protein, human; D012313:RNA
keywords: FHL5; Korea; STXBP2 mutation; familial hemophagocytic lymphohistiocytosis