WASP gene mutations in wiskott-aldrich syndrome and X-linked thrombocytopenia

Jonathan M J Derry, Julie A. Kerns, Kenneth I. Weinberg, Hans D. Ochs, Victor Volpini, Xavier P. Estivill, Ann P. Walker, Uta Francke

Research output: Contribution to journalArticle

122 Citations (Scopus)

Abstract

The WASP gene has been recently cloned from Xp11.23 and shown to be mutated in three patients with the Wiskott-Aldrich syndrome (WAS). We have developed a screening protocol for identifying WASP gene alterations in genomic DNA and have identified a spectrum of novel mutations In 12 additional unrelated families. These missense, nonsense and frameshift mutations involve eight of the 12 exons of the gene. Two mutations creating premature termination codons were associated with lack of detectable mRNA on Northern blots. Four amino acid substitutions, Leu27Phe, Thr48lle, Val75Met and Arg477Lys, were found In patients with congenital thrombocytopenia and no clinically evident immune defect indicating that the WASP gene is the site for mutations in X-linked thrombocytopenia as well as in WAS. A T-cell line from a WAS patient contained two independent DNA alterations, a constitutional frameshift mutation, also present in peripheral blood leukocytes from the patient, and a compensatory splice site mutation unique to the cell line. The distribution of eight missense mutations provides valuable information on amino acids which are essential for normal protein function, and suggests that sites in the first two exons are hot-spots for mutation. / 1995 Oxford University Press.

Original languageEnglish
Pages (from-to)1127-1135
Number of pages9
JournalHuman Molecular Genetics
Volume4
Issue number7
DOIs
Publication statusPublished - Jul 1995
Externally publishedYes

Fingerprint

Wiskott-Aldrich Syndrome
Mutation
Genes
Gene
Frameshift Mutation
Nonsense Codon
Amino acids
Missense Mutation
DNA
Exons
T-cells
Cell Line
Essential Amino Acids
Amino Acids
Amino Acid Substitution
Screening
Blood
Substitution reactions
Thrombocytopenia
Northern Blotting

ASJC Scopus subject areas

  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Public Health, Environmental and Occupational Health
  • Molecular Biology
  • Genetics(clinical)
  • Genetics

Cite this

Derry, J. M. J., Kerns, J. A., Weinberg, K. I., Ochs, H. D., Volpini, V., Estivill, X. P., ... Francke, U. (1995). WASP gene mutations in wiskott-aldrich syndrome and X-linked thrombocytopenia. Human Molecular Genetics, 4(7), 1127-1135. https://doi.org/10.1093/hmg/4.7.1127

WASP gene mutations in wiskott-aldrich syndrome and X-linked thrombocytopenia. / Derry, Jonathan M J; Kerns, Julie A.; Weinberg, Kenneth I.; Ochs, Hans D.; Volpini, Victor; Estivill, Xavier P.; Walker, Ann P.; Francke, Uta.

In: Human Molecular Genetics, Vol. 4, No. 7, 07.1995, p. 1127-1135.

Research output: Contribution to journalArticle

Derry, JMJ, Kerns, JA, Weinberg, KI, Ochs, HD, Volpini, V, Estivill, XP, Walker, AP & Francke, U 1995, 'WASP gene mutations in wiskott-aldrich syndrome and X-linked thrombocytopenia', Human Molecular Genetics, vol. 4, no. 7, pp. 1127-1135. https://doi.org/10.1093/hmg/4.7.1127
Derry, Jonathan M J ; Kerns, Julie A. ; Weinberg, Kenneth I. ; Ochs, Hans D. ; Volpini, Victor ; Estivill, Xavier P. ; Walker, Ann P. ; Francke, Uta. / WASP gene mutations in wiskott-aldrich syndrome and X-linked thrombocytopenia. In: Human Molecular Genetics. 1995 ; Vol. 4, No. 7. pp. 1127-1135.
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