Unusual Mutations in Btk: An Insertion, a Duplication, an Inversion, and Four Large Deletions

doi:10.1006/clim.1998.4629

Clinical Immunology

Volume 90, Issue 1, January 1999, Pages 28-37

https://doi.org/10.1006/clim.1998.4629 Get rights and content

Abstract

Mutations in Bruton's tyrosine kinase (Btk) result in the immunodeficiency X-linked agammaglobulinemia (XLA). In a previous study of 101 patients with presumed XLA, we identified seven patients with large genomic alterations in Btk. The recent completion of 100 kb of contiguous DNA sequence at the Btk locus has allowed us to characterize these mutations in detail and to identify four different types of alterations. These alterations included a 253-bp retroposon insertion at position +5 within intron 9, an inversion of greater than 48 kb that disrupted Btk between exons 4 and 5, a 12.9-kb duplication including Btk exons 2 to 5, and four deletions ranging from 2.8 to 38 kb in size. The duplication and three of the deletions resulted from unequal crossovers of Alu repeats. Further, three of the deletions terminated within a repeat-rich cluster spanning 30 kb of sequence 3′ of Btk exon 19, suggesting that this region was more susceptible to unequal crossovers than the rest of the Btk gene. These studies describe the first reports of an insertion, an inversion, and a duplication in Btk and demonstrate the utility of large-scale sequencing in the elucidation of disease-causing mutations.

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Regular ArticleUnusual Mutations in Btk: An Insertion, a Duplication, an Inversion, and Four Large Deletions

Abstract

Cell

Curr. Opin. Immunol.

Am. J. Hum. Genet.

J. Pediatr.

Mol. Biol.

Cell

Genomics

X-linked agammaglobulinemia: An analysis of 96 patients

Medicine

X-linked agammaglobulinemia: New approaches to old questions based on the identification of the defective gene

Immunol. Rev.

The gene involved in X-linked agammaglobulinemia is a member of thesrc

Nature

itk

Proc. Natl. Acad. Sci. USA

Expression of a novel form ofTecKit

Oncogene

BMX, a novel nonreceptor tyrosine kinase gene of theBTK/ITK/TEC/TXK

Oncogene

The genomic structure of humanBTK

Immunogenetics

Genomic organization of the Btk gene and exon scanning for mutations in patients with X-linked agammaglobulinemia

Hum. Mol. Genet.

Genomic organization and structure of Bruton agammaglobulinemia tyrosine kinase: Localization of mutations associated with varied clinical presentations and course in X chromosome-linked agammaglobulinemia

Proc. Natl. Acad. Sci. USA

Genomic organization of mouse and human Bruton's agammaglobulinemia tyrosine kinase (Btk) loci

J. Immunol.

Large-scale comparative sequence analysis of the human and murine Bruton's tyrosine kinase loci reveals conserved regulatory domains

Genome Res.

BTKbase, mutation database for X-linked agammaglobulinemia (XLA)

Nucleic Acids Res.

Regular Article
Unusual Mutations in Btk: An Insertion, a Duplication, an Inversion, and Four Large Deletions