Molecular analysis of a novel hereditary C3 deficiency with systemic lupus erythematosus

Hiroshi Tsukamoto, Takahiko Horiuchi, Hisashi Kokuba, Shonosuke Nagae, Hiroaki Nishizaka, Takuya Sawabe, Shin Ichi Harashima, Daisuke Himeji, Takako Koyama, Junji Otsuka, Hiroki Mitoma, Yasutaka Kimoto, Chinami Hashimura, Etsuko Kitano, Hajime Kitamura, Masutaka Furue, Mine Harada

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

A case of inherited homozygous complement C3 deficiency (C3D) in a patient with systemic lupus erythematosus (SLE) and the molecular basis for this deficiency are reported. A 22-year-old Japanese male was diagnosed as having SLE and his medical history revealed recurrent tonsillitis and pneumonia. He was diagnosed as having C3D because of undetectable serum C3 level. His parents were consanguineous. Sequence analysis of C3D cDNA revealed a homozygous deletion of exon 39 (84 bp). A single base substitution (AG to GG) in the 3′-splice acceptor site of intron 38 was identified by sequencing the genomic DNA. Expression of C3Δ(ex39) cDNA, the C3cDNA lacking exon 39, in COS-7 cells revealed that C3Δ(ex39) was retained in endoplasmic reticulum-Golgi intermediate compartment because of defective secretion. These data indicate that a novel AG → GG 3′-splice acceptor site mutation in intron 38 caused aberrant splicing of exon 39, resulting in defective secretion of C3.

Original languageEnglish
Pages (from-to)298-304
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume330
Issue number1
DOIs
Publication statusPublished - Apr 29 2005

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this