title: Identification of mutations in the Bruton's tyrosine kinase gene, including a novel genomic rearrangements resulting in large deletion, in Korean X-linked agammaglobulinemia patients.
abstract: Mutations in the Bruton's tyrosine kinase ( BTK) gene are responsible for X-linked agammaglobulinemia (XLA). We identified BTK mutations in six patients with presumed XLA from unrelated Korean families. Four out of six mutations were novel: two missense mutations (P565T, C154Y), a point mutation in a splicing donor site (IVS11+1G>A), and a large deletion (a 6.1-kb deletion including BTK exons 11-18). The large deletion, identified by long-distance PCR, revealed Alu-Alu mediated recombination extended from an Alu sequence in intron 10 to another Alu sequence in intron 18, spanning a distance of 6.1 kb. The two known mutations consisted of one missense (G462D) mutation, and a point mutation in a splicing acceptor site (IVS7-9A>G). This study suggests that large genomic rearrangements involving Alu repeats are few but an important component of the spectrum of BTK mutations.
authors.affiliation: Department of Microbiology, College of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Eun-Kyeong
authors.initials: EK
authors.lastname: Jo
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan. kanegane@ms.toyama-mpu.ac.jp.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kanegane
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Futatani
authors.affiliation: Department of Microbiology, College of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Chang-Hwa
authors.initials: CH
authors.lastname: Song
authors.affiliation: Department of Microbiology, College of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Jeong-Kyu
authors.initials: JK
authors.lastname: Park
authors.affiliation: Department of Pediatrics, Chonbuk National University Medical School, Jeonbuk, Korea.
authors.forename: Jung Soo
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Dong Soo
authors.initials: DS
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Seoul, Korea.
authors.forename: Kang-Mo
authors.initials: KM
authors.lastname: Ahn
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Seoul, Korea.
authors.forename: Sang-Il
authors.initials: SI
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, College of Medicine, Chungbuk National University, Chungbuk, Korea.
authors.forename: Hyeon Jin
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Department of Pediatrics, College of Medicine, Chungbuk National University, Chungbuk, Korea.
authors.forename: Youn Soo
authors.initials: YS
authors.lastname: Hahn
authors.affiliation: Department of Pediatrics, College of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Miyawaki
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000201:enzymology* / Q000235:genetics*; D020087:Alu Elements; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D041321:Chromosomes, Human, X; D008040:Genetic Linkage; D006801:Humans; D007723:Korea; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D020080:Tandem Repeat Sequences
chemical_list: D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human