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.
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.
Jo
Eun-Kyeong
EK
Department of Microbiology, College of Medicine, Chungnam National University, Daejeon, Korea.
Wang
Yue
Y
Department of Pediatrics, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.
Kanegane
Hirokazu
H
Department of Pediatrics, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan. kanegane@ms.toyama-mpu.ac.jp.
Futatani
Takeshi
T
Department of Pediatrics, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.
Song
Chang-Hwa
CH
Department of Microbiology, College of Medicine, Chungnam National University, Daejeon, Korea.
Park
Jeong-Kyu
JK
Department of Microbiology, College of Medicine, Chungnam National University, Daejeon, Korea.
Kim
Jung Soo
JS
Department of Pediatrics, Chonbuk National University Medical School, Jeonbuk, Korea.
Kim
Dong Soo
DS
Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea.
Ahn
Kang-Mo
KM
Department of Pediatrics, Samsung Medical Center, Seoul, Korea.
Lee
Sang-Il
SI
Department of Pediatrics, Samsung Medical Center, Seoul, Korea.
Park
Hyeon Jin
HJ
Department of Pediatrics, College of Medicine, Chungbuk National University, Chungbuk, Korea.
Hahn
Youn Soo
YS
Department of Pediatrics, College of Medicine, Chungbuk National University, Chungbuk, Korea.
Lee
Jae-Ho
JH
Department of Pediatrics, College of Medicine, Chungnam National University, Daejeon, Korea.
Miyawaki
Toshio
T
Department of Pediatrics, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.
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
D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human