TY - JOUR
T1 - Molecular analysis of a novel hereditary C3 deficiency with systemic lupus erythematosus
AU - Tsukamoto, Hiroshi
AU - Horiuchi, Takahiko
AU - Kokuba, Hisashi
AU - Nagae, Shonosuke
AU - Nishizaka, Hiroaki
AU - Sawabe, Takuya
AU - Harashima, Shin Ichi
AU - Himeji, Daisuke
AU - Koyama, Takako
AU - Otsuka, Junji
AU - Mitoma, Hiroki
AU - Kimoto, Yasutaka
AU - Hashimura, Chinami
AU - Kitano, Etsuko
AU - Kitamura, Hajime
AU - Furue, Masutaka
AU - Harada, Mine
N1 - Funding Information:
This work was supported by a Grant-in-Aid from the Ministry of Education, Science, Sports and Culture of Japan (16590984). We thank Dr. David E. Isenman for the C3 cDNA.
PY - 2005/4/29
Y1 - 2005/4/29
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=20144378605&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=20144378605&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2005.02.159
DO - 10.1016/j.bbrc.2005.02.159
M3 - Article
C2 - 15781264
AN - SCOPUS:20144378605
VL - 330
SP - 298
EP - 304
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 1
ER -