In vitro correction of a novel splicing alteration in the BTK gene by using antisense morpholino oligonucleotides

Arch Immunol Ther Exp (Warsz). 2014 Oct;62(5):431-6. doi: 10.1007/s00005-014-0283-0. Epub 2014 Mar 23.

Abstract

A novel sequence variant, c.240+109C>A, in the Bruton's tyrosine kinase (BTK) gene was identified in a patient with X-linked agammaglobulinemia. This alteration resulted in an incorporation of 106 nucleotides of BTK intron 3 into its mRNA. Administration of the 25-mer antisense morpholino oligonucleotide analog in the patient's cultured peripheral blood mononuclear cells was able to restore correctly spliced BTK mRNA, a potential treatment for X-linked agammaglobulinemia.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agammaglobulinaemia Tyrosine Kinase
  • Agammaglobulinemia / diagnosis*
  • Agammaglobulinemia / genetics
  • Agammaglobulinemia / therapy
  • Base Sequence
  • Cells, Cultured
  • Child, Preschool
  • Genetic Diseases, X-Linked / diagnosis*
  • Genetic Diseases, X-Linked / genetics
  • Genetic Diseases, X-Linked / therapy
  • Genetic Therapy
  • Humans
  • In Vitro Techniques
  • Introns / genetics
  • Leukocytes, Mononuclear / physiology*
  • Male
  • Molecular Sequence Data
  • Morpholinos / genetics
  • Mutagenesis, Insertional / genetics
  • Oligoribonucleotides, Antisense / genetics
  • Polymorphism, Genetic
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*
  • RNA Splicing / genetics
  • Thailand

Substances

  • Morpholinos
  • Oligoribonucleotides, Antisense
  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase
  • BTK protein, human

Supplementary concepts

  • Bruton type agammaglobulinemia