title: Molecular analysis of a novel hereditary C3 deficiency with systemic lupus erythematosus.
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 (84bp). 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 C3Delta(ex39) cDNA, the C3cDNA lacking exon 39, in COS-7 cells revealed that C3Delta(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.
authors.affiliation: Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka 812-8582, Japan. tsukamot@intmed1.med.kyushu-u.ac.jp <tsukamot@intmed1.med.kyushu-u.ac.jp>
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tsukamoto
authors.forename: Takahiko
authors.initials: T
authors.lastname: Horiuchi
authors.forename: Hisashi
authors.initials: H
authors.lastname: Kokuba
authors.forename: Shonosuke
authors.initials: S
authors.lastname: Nagae
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nishizaka
authors.forename: Takuya
authors.initials: T
authors.lastname: Sawabe
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Harashima
authors.forename: Daisuke
authors.initials: D
authors.lastname: Himeji
authors.forename: Takako
authors.initials: T
authors.lastname: Koyama
authors.forename: Junji
authors.initials: J
authors.lastname: Otsuka
authors.forename: Hiroki
authors.initials: H
authors.lastname: Mitoma
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Kimoto
authors.forename: Chinami
authors.initials: C
authors.lastname: Hashimura
authors.forename: Etsuko
authors.initials: E
authors.lastname: Kitano
authors.forename: Hajime
authors.initials: H
authors.lastname: Kitamura
authors.forename: Masutaka
authors.initials: M
authors.lastname: Furue
authors.forename: Mine
authors.initials: M
authors.lastname: Harada
mesh_terms: D000328:Adult; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D003176:Complement C3 / Q000172:deficiency* / Q000235:genetics; D017931:DNA Primers; D005455:Fluorescent Antibody Technique; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D003176:Complement C3; D017931:DNA Primers; D012333:RNA, Messenger