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

J Hum Genet. 2003;48(6):322-326. doi: 10.1007/s10038-003-0032-4. Epub 2003 May 24.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agammaglobulinaemia Tyrosine Kinase
  • Agammaglobulinemia / enzymology*
  • Agammaglobulinemia / genetics*
  • Alu Elements
  • Base Sequence
  • Child
  • Child, Preschool
  • Chromosomes, Human, X*
  • Genetic Linkage
  • Humans
  • Korea
  • Male
  • Molecular Sequence Data
  • Mutation*
  • Protein-Tyrosine Kinases / genetics*
  • Tandem Repeat Sequences

Substances

  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase
  • BTK protein, human