Early-onset sarcoidosis and CARD15 mutations with constitutive nuclear factor-kappaB activation: common genetic etiology with Blau syndrome.

Abstract

Early-onset sarcoidosis (EOS) and inheritable Blau syndrome (BS) share characteristic clinical features of juvenile-onset systemic granulomatosis syndrome that mainly affects skin, joints, and eyes. However, no direct evidence has been shown for the possible common origin of these 2 diseases. Recent discovery of CARD15 mutations in BS families encouraged us to investigate similar CARD15 mutations in EOS patients. Among 10 EOS cases retrospectively collected in Japan, heterozygous missense mutations were found in 9 cases; 4 showed a 1000C>T (R334W in amino acid change) that has been reported in BS, 4 showed novel 1487A>T (H496L), 1538T>C (M513T), 1813A>C (T605P), and 2010C>A (N670K), and 1 case showed double 1146C>G (D382E)/1834G>A (A612T) mutations on different alleles. All 6 of these variants of CARD15 showed increased basal nuclear factor (NF)-kappaB activity. These findings indicate that the majority of EOS and BS cases share the common genetic etiology of CARD15 mutations that cause constitutive NF-kappaB activation.

• Authors: Nobuo Kanazawa, Ikuo Okafuji, Naotomo Kambe, Ryuta Nishikomori, Mami Nakata-Hizume, Sonoko Nagai, Akihiko Fuji, Takenosuke Yuasa, Akira Manki, Yoshihiko Sakurai, Mitsuru Nakajima, Hiroko Kobayashi, Ikuma Fujiwara, Hiroyuki Tsutsumi, Atsushi Utani, Chikako Nishigori, Toshio Heike, Tatsutoshi Nakahata, Yoshiki Miyachi
• Journal: Blood (Blood) Vol. 105 Issue 3 Pg. 1195-7 (Feb 01 2005) ISSN: 0006-4971 [Print] United States
• PMID: 15459013 (Publication Type: Journal Article)

Chemical References

• Intracellular Signaling Peptides and Proteins
• NF-kappa B
• NOD2 protein, human
• Nod2 Signaling Adaptor Protein

Topics

• Age of Onset
• Crohn Disease (genetics)
• Exanthema (genetics)
• Gene Expression Regulation
• Glaucoma, Angle-Closure (genetics)
• Humans
• Intracellular Signaling Peptides and Proteins (genetics)
• Mutation
• NF-kappa B (genetics, metabolism)
• Nod2 Signaling Adaptor Protein
• Polymorphism, Single Nucleotide (genetics)
• Sarcoidosis (genetics)
• Syndrome