High-Incidence of C9 Deficiency throughout Japan: There Are No Significant Differences in Incidence among Eight Areas of Japan

Hayama, Kenji; Sugai, Nagae; Tanaka, Shoji; Lee, Shiei; Kikuchi, Hiroaki; Ito, Jin; Suzuki, Junzo; Nagata, Y.; Kondo, Hozumi; Harayama, Osamu; Tuzuki, Kazuo; Shoji, Yasuhiro; Fujita, Mitsue; Ohmori, Fumihiko; Kawai, Tadashi; Akagaki, Yohji; Inai, Shinya

doi:10.1159/000235061

Cited by 32 publications

(21 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The estimated frequency of the C9 deficiency with the homozygous Arg95Stop mutation in our hospitalbased DNA study was 0.12%, which was similar to the frequencies of the C9 deficiency determined by serum studies, including both hospital-based (Hayama et al 1989) and blood donor-based (Fukumori et al 1989) studies. There were no significant differences in the incidence of C9 deficiency among the eight areas of the four main islands in Japan (Hayama et al 1989). We identified an equal frequency of Arg95Stop heterozygotes in two areas in two of the four main islands.…”

Section: Resultssupporting

confidence: 80%

“…In Japan, it is one of the most frequent genetic disorders, with its incidence being approximately one in 1000 (Hayama et al 1989;Fukumori et al 1989), whereas only a few patients with C9 deficiency have been identified in European countries. Although most individuals with C9 deficiency appear to be healthy, our previous study ) demonstrated that the risk of development of meningococcal meningitis in C9-deficient individuals was much higher than that in normal individuals, based on the incidence of C9 deficiency among blood donors in Fukuoka and the number of C9-deficient individuals in that area who developed meningococcal meningitis.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Molecular epidemiology of C9 deficiency heterozygotes with an Arg95Stop mutation of the C9 gene in Japan

et al. 1999

View full text Add to dashboard Cite

Deficiency of the ninth component of human complement (C9) is the most common complement deficiency in Japan, with an incidence of approximately one homozygote in 1000, but is very rare in other countries. Genetic analyses of Japanese C9 deficiency have shown that a C-to-T transition leading to TGA stop codon for Arg95 in exon 4 of the C9 gene (Arg95Stop) is common in Japanese C9 deficiency. To determine the prevalence of heterozygous carriers of the Arg95Stop mutation in a Japanese population, we collected DNA samples from 300 individuals in two of the four main islands of Japan. Heterozygote detection was performed with an allele-specific polymerase chain reaction (PCR) system designed to detect exclusively only one of the normal and mutant alleles, followed by confirmation with PCR/single-strand conformation polymorphism (SSCP) analysis and direct sequencing. Twenty individuals were heterozygous for the Arg95Stop mutation. None was homozygous. The prevalence of carriers of the Arg95Stop mutation was 6.7% (20/300). An estimated frequency (0.12%) of complete C9 deficiency due to homozygous Arg95Stop mutation was consistent with frequencies determined by serological studies.

show abstract

Section: Resultssupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Molecular epidemiology of C9 deficiency heterozygotes with an Arg95Stop mutation of the C9 gene in Japan

et al. 1999

View full text Add to dashboard Cite

show abstract

“…These data were obtained from large-scale screening of blood donors or hospitalized patients (144,183,201). Most deficiencies result from point mutations that result in premature stop codons (484).…”

Section: Inherited Deficiencies Of Complement Activationmentioning

confidence: 99%

Infections of People with Complement Deficiencies and Patients Who Have Undergone Splenectomy

2010

View full text Add to dashboard Cite

SUMMARY The complement system comprises several fluid-phase and membrane-associated proteins. Under physiological conditions, activation of the fluid-phase components of complement is maintained under tight control and complement activation occurs primarily on surfaces recognized as “nonself” in an attempt to minimize damage to bystander host cells. Membrane complement components act to limit complement activation on host cells or to facilitate uptake of antigens or microbes “tagged” with complement fragments. While this review focuses on the role of complement in infectious diseases, work over the past couple of decades has defined several important functions of complement distinct from that of combating infections. Activation of complement in the fluid phase can occur through the classical, lectin, or alternative pathway. Deficiencies of components of the classical pathway lead to the development of autoimmune disorders and predispose individuals to recurrent respiratory infections and infections caused by encapsulated organisms, including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae. While no individual with complete mannan-binding lectin (MBL) deficiency has been identified, low MBL levels have been linked to predisposition to, or severity of, several diseases. It appears that MBL may play an important role in children, who have a relatively immature adaptive immune response. C3 is the point at which all complement pathways converge, and complete deficiency of C3 invariably leads to severe infections, including those caused by meningococci and pneumococci. Deficiencies of the alternative and terminal complement pathways result in an almost exclusive predisposition to invasive meningococcal disease. The spleen plays an important role in antigen processing and the production of antibodies. Splenic macrophages are critical in clearing opsonized encapsulated bacteria (such as pneumococci, meningococci, and Escherichia coli) and intraerythrocytic parasites such as those causing malaria and babesiosis, which explains the fulminant nature of these infections in persons with anatomic or functional asplenia. Paramount to the management of patients with complement deficiencies and asplenia is educating patients about their predisposition to infection and the importance of preventive immunizations and seeking prompt medical attention.

show abstract

“…Among 145,640 donors in the Osaka area (Japan), we found 2 cases with inherited C5D, 4 with C6D, 6 with C7D, 4 with C8 ·-Á subunit deficiency (C8·-ÁD) and 138 with C9D with an indcidence of 0.0014, 0.0027, 0.0041, 0.0027 and 0.0948%, respectively [4,5]. Hayama et al [6] reported that among 92,686 sera from hospitalized patients throughout Japan, 80 were found to be deficient in C9 using the same screening system. The incidence of C9D nationwide was determined to be about 0.086%, and no significant differences were observed among the 8 areas of Japan tested [6].…”

mentioning

confidence: 87%

“…Hayama et al [6] reported that among 92,686 sera from hospitalized patients throughout Japan, 80 were found to be deficient in C9 using the same screening system. The incidence of C9D nationwide was determined to be about 0.086%, and no significant differences were observed among the 8 areas of Japan tested [6]. It is concluded that the incidence of homozygous C9D is almost 1 in 1,000 in Japan.…”

mentioning

confidence: 99%

Terminal Complement Component Deficiencies in Japan

Fukumori

Horiuchi

1998

Exp Clin Immunogenet

View full text Add to dashboard Cite

From the serological screening for complement component deficiencies, we found 2 subjects with inherited C5 deficiency (C5D), 4 with C6D, 6 with C7D, 4 with C81 (α-γ subunit) D and 138 with C9D among 145,640 healthy Japanese blood donors. Recently, the genetic bases of some of the C6D, C7D, C81D and C9D Japanese individuals were elucidated using an exon-specific PCR-SSCP method followed by direct sequencing of the target exons.

show abstract

High-Incidence of C9 Deficiency throughout Japan: There Are No Significant Differences in Incidence among Eight Areas of Japan

Cited by 32 publications

References 2 publications

Molecular epidemiology of C9 deficiency heterozygotes with an Arg95Stop mutation of the C9 gene in Japan

Molecular epidemiology of C9 deficiency heterozygotes with an Arg95Stop mutation of the C9 gene in Japan

Infections of People with Complement Deficiencies and Patients Who Have Undergone Splenectomy

Terminal Complement Component Deficiencies in Japan

Contact Info

Product

Resources

About