Human Genetics

, Volume 103, Issue 1, pp 81–85

Direct evidence of autosomal recessive inheritance of Arg24 to termination codon in purine nucleoside phosphorylase gene in a family with a severe combined immunodeficiency patient

Authors

  • Y. Sasaki
    • Department of Safety Research on Biologics, National Institute of Infectious Diseases, 4-7-1, Gakuen, Musashimurayama, Tokyo, 208, Japan e-mail: yuko@nih.go.jp, Tel.: +81-425-61-0771 (ext. 555), Fax: +81-425-65-3315
  • Mikiro Iseki
    • Department of Pediatrics, Tokyo Metropolitan Otsuka Hospital, 2-8-1, Minamiotsuka, Toshimaku, Tokyo, 170, Japan
  • Shinya Yamaguchi
    • Department of Pediatrics, Kitasato Institute Hospital, 5-9-1, Shirogane, Minatoku, Tokyo, 108, Japan
  • Yoshihiro Kurosawa
    • Department of Pediatrics, Keio University School of Medicine, 35, Shinanomashi, Shinjyukuku, Tokyo, 160, Japan
  • Tetsuya Yamamoto
    • Third Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawacho, Nishinomiya, Hyogo, 663, Japan
  • Yuji Moriwaki
    • Third Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawacho, Nishinomiya, Hyogo, 663, Japan
  • Tsuyoshi Kenri
    • Department of Safety Research on Biologics, National Institute of Infectious Diseases, 4-7-1, Gakuen, Musashimurayama, Tokyo, 208, Japan e-mail: yuko@nih.go.jp, Tel.: +81-425-61-0771 (ext. 555), Fax: +81-425-65-3315
  • Tsuguo Sasaki
    • Department of Safety Research on Biologics, National Institute of Infectious Diseases, 4-7-1, Gakuen, Musashimurayama, Tokyo, 208, Japan e-mail: yuko@nih.go.jp, Tel.: +81-425-61-0771 (ext. 555), Fax: +81-425-65-3315
  • Ryoko Yamashita
    • Department of Pediatrics, Kitasato Institute Hospital, 5-9-1, Shirogane, Minatoku, Tokyo, 108, Japan
Original investigation

DOI: 10.1007/s004390050787

Cite this article as:
Sasaki, Y., Iseki, M., Yamaguchi, S. et al. Hum Genet (1998) 103: 81. doi:10.1007/s004390050787

Abstract

Purine nucleoside phosphorylase (PNP) deficiency is a rare immunodeficiency disease involving a T-lymphocyte-dysfunction that is fatal unless bone marrow transplantation is successful. In this study we undertook genetic analysis of a patient with PNP deficiency. Sequencing of the PNP gene, which is located on chromosome 14q13, of the patient led to the identification of three point mutations in exon 2 at amino acid positions 20 (His, silent mutation), 24 (Arg→termination codon) and 51 (Ser→Gly). Intrafamilial sequence analysis of exon 2 revealed that both parents were heterozygous for the Arg24 and termination codon 24 alleles. Two of their three children had inherited different homozygous alleles, termination codon 24 for the patient, and Arg24 for his healthy sibling. Transcriptional termination was suggested as the mechanism giving rise to the disorder in this case. A lack of PNP protein was also confirmed by immunoblot analysis of the patient’s hemolysate. This could be the first report providing evidence of autosomal recessive inheritance in PNP deficiency by sequence-based analysis.

Copyright information

© Springer-Verlag Berlin Heidelberg 1998