Chinami Hashimura

Publications (2)4.46 Total impact

• Article: 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
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  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.
  Biochemical and Biophysical Research Communications 04/2005; 330(1):298-304. · 2.48 Impact Factor
• Article: Novel mutations in TNFRSF1A in patients with typical tumor necrosis factor receptor-associated periodic syndrome and with systemic lupus erythematosus in Japanese.

  Takahiko Horiuchi, Hiroshi Tsukamoto, Hiroki Mitoma, Hiroshi Miyagawa, Yasuhiro Tamimoto, Seiji Yoshizawa, Mine Harada, Kenshi Hayashi, Chinami Hashimura, Motohiro Oribe, Seiichi Okamura
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  ABSTRACT: Molecular defects of TNFRSF1A was investigated in members of a family presenting with typical phenotypes of tumor necrosis factor receptor-associated periodic syndrome (TRAPS) and in patients with the autoimmune disorders, systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Genomic DNA from the members of a family with typical TRAPS, as well as from 100 patients with SLE, 100 patients with RA and 100 healthy individuals, was studied for mutations in exons 2, 3 and 4 of the TNFRSF1A gene. All individuals were Japanese. Three novel missense mutations were identified in the TNFRSF1A. The C70G mutation was identified in family members with typical TRAPS, which was the second case in eastern Asian population. In addition, the T61I and R104Q mutations were each identified in 2 of the 100 SLE patients. The T61I mutation was identified in one of the 100 healthy individuals. No mutations were identified in the 100 RA patients. Functional analysis revealed that PMA-induced shedding of TNFRSF1A from PBMCs was impaired in a patient carrying T61I. A larger scale of study will clarify whether these two mutations, T61I and R104Q, are associated with chronic inflammatory disorders, such as SLE, or not.
  International Journal of Molecular Medicine 12/2004; 14(5):813-8. · 1.98 Impact Factor