Skip to main content

Adenosine deaminase deficiency with mosaicism for a "second-site suppressor" of a splicing mutation: decline in revertant T lymphocytes during enzyme replacement therapy.

Publication ,  Journal Article
Arredondo-Vega, FX; Santisteban, I; Richard, E; Bali, P; Koleilat, M; Loubser, M; Al-Ghonaium, A; Al-Helali, M; Hershfield, MS
Published in: Blood
February 1, 2002

Four patients from 3 Saudi Arabian families had delayed onset of immune deficiency due to homozygosity for a novel intronic mutation, g.31701T>A, in the last splice acceptor site of the adenosine deaminase (ADA) gene. Aberrant splicing mutated the last 4 ADA amino acids and added a 43-residue "tail" that rendered the protein unstable. Mutant complementary DNA (cDNA) expressed in Escherichia coli yielded 1% of the ADA activity obtained with wild-type cDNA. The oldest patient, 16 years old at diagnosis, had greater residual immune function and less elevated erythrocyte deoxyadenosine nucleotides than his 4-year-old affected sister. His T cells and Epstein-Barr virus (EBV) B cell line had 75% of normal ADA activity and ADA protein of normal size. DNA from these cells and his whole blood possessed 2 mutant ADA alleles. Both carried g.31701T>A, but one had acquired a deletion of the 11 adjacent base pair, g.31702-12, which suppressed aberrant splicing and excised an unusual purine-rich tract from the wild-type intron 11/exon 12 junction. During ADA replacement therapy, ADA activity in T cells and abundance of the "second-site" revertant allele decreased markedly. This finding raises an important issue relevant to stem cell gene therapy.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Blood

DOI

ISSN

0006-4971

Publication Date

February 1, 2002

Volume

99

Issue

3

Start / End Page

1005 / 1013

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Severe Combined Immunodeficiency
  • Saudi Arabia
  • RNA Splice Sites
  • Mutation
  • Mosaicism
  • Male
  • Infant
  • Immunology
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Arredondo-Vega, F. X., Santisteban, I., Richard, E., Bali, P., Koleilat, M., Loubser, M., … Hershfield, M. S. (2002). Adenosine deaminase deficiency with mosaicism for a "second-site suppressor" of a splicing mutation: decline in revertant T lymphocytes during enzyme replacement therapy. Blood, 99(3), 1005–1013. https://doi.org/10.1182/blood.v99.3.1005
Arredondo-Vega, Francisco X., Ines Santisteban, Eva Richard, Pawan Bali, Majed Koleilat, Michael Loubser, Abdulaziz Al-Ghonaium, Mariam Al-Helali, and Michael S. Hershfield. “Adenosine deaminase deficiency with mosaicism for a "second-site suppressor" of a splicing mutation: decline in revertant T lymphocytes during enzyme replacement therapy.Blood 99, no. 3 (February 1, 2002): 1005–13. https://doi.org/10.1182/blood.v99.3.1005.
Arredondo-Vega FX, Santisteban I, Richard E, Bali P, Koleilat M, Loubser M, et al. Adenosine deaminase deficiency with mosaicism for a "second-site suppressor" of a splicing mutation: decline in revertant T lymphocytes during enzyme replacement therapy. Blood. 2002 Feb 1;99(3):1005–13.
Arredondo-Vega, Francisco X., et al. “Adenosine deaminase deficiency with mosaicism for a "second-site suppressor" of a splicing mutation: decline in revertant T lymphocytes during enzyme replacement therapy.Blood, vol. 99, no. 3, Feb. 2002, pp. 1005–13. Pubmed, doi:10.1182/blood.v99.3.1005.
Arredondo-Vega FX, Santisteban I, Richard E, Bali P, Koleilat M, Loubser M, Al-Ghonaium A, Al-Helali M, Hershfield MS. Adenosine deaminase deficiency with mosaicism for a "second-site suppressor" of a splicing mutation: decline in revertant T lymphocytes during enzyme replacement therapy. Blood. 2002 Feb 1;99(3):1005–1013.

Published In

Blood

DOI

ISSN

0006-4971

Publication Date

February 1, 2002

Volume

99

Issue

3

Start / End Page

1005 / 1013

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Severe Combined Immunodeficiency
  • Saudi Arabia
  • RNA Splice Sites
  • Mutation
  • Mosaicism
  • Male
  • Infant
  • Immunology
  • Humans