Journal of the Korean Pediatric Society 2002;45(3):302-310.
Published online March 15, 2002.
Characterization of Mutations in Bruton's Tyrosine Kinase(Btk) Gene from Unrelated 3 X-linked Agammaglobulinemia(XLA) Families in Korea
Chang-Hwa Song1, Eun-Kyeong Jo1, Jeong-Kyu Park1, Jung-Soo Kim2, Soo-Jong Hong3, Jae-Ho Lee4
1Department of Microbiology, College of Medicine, Chungnam National University, Taejon, Korea
2Department of Pediatrics, College of Medicine, Chungnam National University, Taejon, Korea
3Department of Pediatrics, College of Medicine, Chunbuk National University, Chunju, Korea
4Department of Pediatrics, Asan Medical Center, College of Medicine, Ulsan University, Seoul, Korea
국내 X-관련성 범저감마글로불린혈증 세가족에 대한 Bruton's Tyrosine Kinase단백질 발현 및 유전자 변이 분석
송창화1, 조은경1, 박정규1, 김정수2, 홍수종3, 이재호4
1충남대학교 의과대학 미생물학교실
2충남대학교 의과대학 소아과학교실
3전북대학교 의과대학 소아과학교실
4울산대학교 의과대학 소아과학교실
Correspondence: 
Jae-Ho Lee, Email: immlee@cnu.ac.kr
Abstract
Purpose
: X-linked agammaglobulinemia(XLA) is an immunodeficiency caused by abnormalities in Bruton's tyrosine kinase(Btk), and is characterized by a deficiency of peripheral blood B cells. We studied cytoplasmic expression of Btk protein and analyzed the Btk gene in peripheral blood mononuclear cells(PBMC) from three XLA families in Korea.
Methods
: Heparinized venous blood samples were collected from four XLA patients and additional family members in three unrelated XLA families. Mononuclear cells were separated from their blood and the intracellular Btk protein was characterized by a flow cytometry. The mutation analysis was performed using direct sequencing.
Results
: Cytoplasmic expression of Btk protein in monocytes was not detected in the patients with XLA. We observed a novel deletion and two point mutations within introns(intron 1 and intron 18) resulting in alternative splicings. In XLA family 2, a 980 bp deletion(from intron 9+191 T to intron 10-215 C) including exon 10 was found in patient P2. He was the only sporadic case in this study, because his mother and brother showed a normal Btk expression by flow cytometry.
Conclusion
: These identified genetic alterations support the molecular heterogeneity of Btk gene in XLA disease. Additionally, by means of flow cytometric analysis, we diagnosed three hypogammaglobulinemia patients as XLA. Advancements in diagnostic methods has facilitated a prompt and definite diagnosis of this disease.
Key Words: Bruton's tyrosine kinase, X-linked agammaglobulinemia, Direct sequencing, Flow cytometry, Carrier detection


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