Human Genetics

, Volume 103, Issue 4, pp 415–418

Selective complement C1s deficiency caused by homozygous four-base deletion in the C1s gene

Authors

  • Naokazu Inoue
    • Division of Biology and Oncology, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263–8555, Japan e-mail: sakiyama@nirs.go.jp, Tel.: +81 43 251 2111, Fax: +81 43 2514593
  • Toshiyuki Saito
    • Genome Research Group, National Institute of Radiological Science, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan
  • Riako Masuda
    • Division of Biology and Oncology, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263–8555, Japan e-mail: sakiyama@nirs.go.jp, Tel.: +81 43 251 2111, Fax: +81 43 2514593
  • Yoshio Suzuki
    • Faculty of Home Economics, Otsuma Women’s University, 12 Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan
  • Michiko Ohtomi
    • Department of Biomolecular Science, Faculty of Science, Toho University, 2-2-1 Miyama, Funabashi-shi, Chiba 274-0072, Japan
  • H. Sakiyama
    • Division of Biology and Oncology, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263–8555, Japan e-mail: sakiyama@nirs.go.jp, Tel.: +81 43 251 2111, Fax: +81 43 2514593
Original investigation

DOI: 10.1007/s004390050843

Cite this article as:
Inoue, N., Saito, T., Masuda, R. et al. Hum Genet (1998) 103: 415. doi:10.1007/s004390050843

Abstract

The complement system plays an important role in defense mechanisms by promoting the adherence of microorganisms to phagocytic cells and lysis of foreign organisms. Deficiencies of the first complement components, C1r/C1s, often cause systemic lupus erythema-tosus-like syndromes and severe pyogenic infections. Up to now no genetic analysis of the C1r/C1s deficiencies has been carried out. In the present work, we report the first genetic analysis of selective C1s deficiency, the patient having a normal amount of C1r. C1s RNA with a normal size was detected in patient’s subcutaneous fibroblasts (YKF) by RNA blot analysis and RT-PCR. The amount of C1s RNA was approximately one-tenth of the RNA from the human chondrosarcoma cell line, HCS2/8. In contrast, the levels of C1r and β-actin RNA of YKF were similar to that of HCS2/8. Sequence analysis of C1s cDNA revealed a deletion at nucleotides 1087–1090 (TTTG), creating a stop codon (TGA) at position 94 downstream of the mutation site. Direct sequencing of the gene between the primers designed on intron 9 and exon 10 indicated the presence of the deletion on exon 10 of the gene. Quantitative Southern blot hybridization suggested the mutation was homozygous. The 4-bp deletion on exon 10 was also found in the patient’s heterozygous mother who had normal hemolytic activity.

Copyright information

© Springer-Verlag Berlin Heidelberg 1998