Genomic organization and structure of Bruton agammaglobulinemia tyrosine kinase

Localization of mutations associated with varied clinical presentations and course in X chromosome-linked agammaglobulinemia

Yuko Ohta, Robert N. Haire, Ronda T. Litman, Shu Man Fu, Robert Nelson, Jamie Kratz, Stephen J. Kornfeld, Maite De La Morena, Robert A. Good, Gary W. Litman

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

X chromosome-linked agammaglobulinemia is a life-threatening disease that involves a failure in normal development of B lymphocytes and is associated with missense mutations in BTK, a gene encoding a cytoplasmic tyrosine kinase (Bruton agammaglobulinemia tyrosine kinase, EC 2.7.1.112), a member of the Tec family of protein-tyrosine kinases. The genomic organization has been determined by using conventional restriction fragment mapping, extended DNA sequencing, and PCR fragment-sizing approaches. The DNA sequences of the 18 coding exons composing BTK and their flanking-region sequences are reported; an additional exon(s) encodes a 5′ untranslated segment. Single-base-pair substitutions and 4-nt deletions resulted in amino acid replacement, premature termination, frameshift, and exon deletion in a group of X chromosome-linked agammaglobulinemia patients exhibiting different clinical presentations and courses. The nature of the mutations is interpreted in terms of the genomic organization of the BTK gene and the disease course in individual patients. Several examples are found in which the same mutation occurs in unrelated patients, and one of these mutations occurs at the same codon that is substituted in the murine form of BTK, resulting in X chromosome-linked immunodeficiency disease. Considerable variation in presentation and disease course in X chromosome-linked agammaglobulinemia appears associated with the nature and position of different missense mutations.

Original languageEnglish (US)
Pages (from-to)9062-9066
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number19
StatePublished - Sep 13 1994
Externally publishedYes

Fingerprint

X Chromosome
Mutation
Exons
Missense Mutation
X-Linked Combined Immunodeficiency Diseases
Restriction Mapping
DNA Sequence Analysis
Codon
Base Pairing
Genes
B-Lymphocytes
Bruton type agammaglobulinemia
Amino Acids
Polymerase Chain Reaction

Keywords

  • DNA sequencing
  • Missense mutation
  • PCR
  • Primary immunodeficiency disease
  • Protein-tyrosine kinase

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

Genomic organization and structure of Bruton agammaglobulinemia tyrosine kinase : Localization of mutations associated with varied clinical presentations and course in X chromosome-linked agammaglobulinemia. / Ohta, Yuko; Haire, Robert N.; Litman, Ronda T.; Fu, Shu Man; Nelson, Robert; Kratz, Jamie; Kornfeld, Stephen J.; De La Morena, Maite; Good, Robert A.; Litman, Gary W.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 91, No. 19, 13.09.1994, p. 9062-9066.

Research output: Contribution to journalArticle

Ohta, Yuko ; Haire, Robert N. ; Litman, Ronda T. ; Fu, Shu Man ; Nelson, Robert ; Kratz, Jamie ; Kornfeld, Stephen J. ; De La Morena, Maite ; Good, Robert A. ; Litman, Gary W. / Genomic organization and structure of Bruton agammaglobulinemia tyrosine kinase : Localization of mutations associated with varied clinical presentations and course in X chromosome-linked agammaglobulinemia. In: Proceedings of the National Academy of Sciences of the United States of America. 1994 ; Vol. 91, No. 19. pp. 9062-9066.
@article{8862b9f46311479794f189b768bb478f,
title = "Genomic organization and structure of Bruton agammaglobulinemia tyrosine kinase: Localization of mutations associated with varied clinical presentations and course in X chromosome-linked agammaglobulinemia",
abstract = "X chromosome-linked agammaglobulinemia is a life-threatening disease that involves a failure in normal development of B lymphocytes and is associated with missense mutations in BTK, a gene encoding a cytoplasmic tyrosine kinase (Bruton agammaglobulinemia tyrosine kinase, EC 2.7.1.112), a member of the Tec family of protein-tyrosine kinases. The genomic organization has been determined by using conventional restriction fragment mapping, extended DNA sequencing, and PCR fragment-sizing approaches. The DNA sequences of the 18 coding exons composing BTK and their flanking-region sequences are reported; an additional exon(s) encodes a 5′ untranslated segment. Single-base-pair substitutions and 4-nt deletions resulted in amino acid replacement, premature termination, frameshift, and exon deletion in a group of X chromosome-linked agammaglobulinemia patients exhibiting different clinical presentations and courses. The nature of the mutations is interpreted in terms of the genomic organization of the BTK gene and the disease course in individual patients. Several examples are found in which the same mutation occurs in unrelated patients, and one of these mutations occurs at the same codon that is substituted in the murine form of BTK, resulting in X chromosome-linked immunodeficiency disease. Considerable variation in presentation and disease course in X chromosome-linked agammaglobulinemia appears associated with the nature and position of different missense mutations.",
keywords = "DNA sequencing, Missense mutation, PCR, Primary immunodeficiency disease, Protein-tyrosine kinase",
author = "Yuko Ohta and Haire, {Robert N.} and Litman, {Ronda T.} and Fu, {Shu Man} and Robert Nelson and Jamie Kratz and Kornfeld, {Stephen J.} and {De La Morena}, Maite and Good, {Robert A.} and Litman, {Gary W.}",
year = "1994",
month = "9",
day = "13",
language = "English (US)",
volume = "91",
pages = "9062--9066",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "19",

}

TY - JOUR

T1 - Genomic organization and structure of Bruton agammaglobulinemia tyrosine kinase

T2 - Localization of mutations associated with varied clinical presentations and course in X chromosome-linked agammaglobulinemia

AU - Ohta, Yuko

AU - Haire, Robert N.

AU - Litman, Ronda T.

AU - Fu, Shu Man

AU - Nelson, Robert

AU - Kratz, Jamie

AU - Kornfeld, Stephen J.

AU - De La Morena, Maite

AU - Good, Robert A.

AU - Litman, Gary W.

PY - 1994/9/13

Y1 - 1994/9/13

N2 - X chromosome-linked agammaglobulinemia is a life-threatening disease that involves a failure in normal development of B lymphocytes and is associated with missense mutations in BTK, a gene encoding a cytoplasmic tyrosine kinase (Bruton agammaglobulinemia tyrosine kinase, EC 2.7.1.112), a member of the Tec family of protein-tyrosine kinases. The genomic organization has been determined by using conventional restriction fragment mapping, extended DNA sequencing, and PCR fragment-sizing approaches. The DNA sequences of the 18 coding exons composing BTK and their flanking-region sequences are reported; an additional exon(s) encodes a 5′ untranslated segment. Single-base-pair substitutions and 4-nt deletions resulted in amino acid replacement, premature termination, frameshift, and exon deletion in a group of X chromosome-linked agammaglobulinemia patients exhibiting different clinical presentations and courses. The nature of the mutations is interpreted in terms of the genomic organization of the BTK gene and the disease course in individual patients. Several examples are found in which the same mutation occurs in unrelated patients, and one of these mutations occurs at the same codon that is substituted in the murine form of BTK, resulting in X chromosome-linked immunodeficiency disease. Considerable variation in presentation and disease course in X chromosome-linked agammaglobulinemia appears associated with the nature and position of different missense mutations.

AB - X chromosome-linked agammaglobulinemia is a life-threatening disease that involves a failure in normal development of B lymphocytes and is associated with missense mutations in BTK, a gene encoding a cytoplasmic tyrosine kinase (Bruton agammaglobulinemia tyrosine kinase, EC 2.7.1.112), a member of the Tec family of protein-tyrosine kinases. The genomic organization has been determined by using conventional restriction fragment mapping, extended DNA sequencing, and PCR fragment-sizing approaches. The DNA sequences of the 18 coding exons composing BTK and their flanking-region sequences are reported; an additional exon(s) encodes a 5′ untranslated segment. Single-base-pair substitutions and 4-nt deletions resulted in amino acid replacement, premature termination, frameshift, and exon deletion in a group of X chromosome-linked agammaglobulinemia patients exhibiting different clinical presentations and courses. The nature of the mutations is interpreted in terms of the genomic organization of the BTK gene and the disease course in individual patients. Several examples are found in which the same mutation occurs in unrelated patients, and one of these mutations occurs at the same codon that is substituted in the murine form of BTK, resulting in X chromosome-linked immunodeficiency disease. Considerable variation in presentation and disease course in X chromosome-linked agammaglobulinemia appears associated with the nature and position of different missense mutations.

KW - DNA sequencing

KW - Missense mutation

KW - PCR

KW - Primary immunodeficiency disease

KW - Protein-tyrosine kinase

UR - http://www.scopus.com/inward/record.url?scp=0028592706&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028592706&partnerID=8YFLogxK

M3 - Article

VL - 91

SP - 9062

EP - 9066

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 19

ER -