Early-onset sarcoidosis and CARD15 mutations with constitutive nuclear factor-κB activation:: common genetic etiology with Blau syndrome
Early-onset sarcoidosis and CARD15 mutations with constitutive nuclear factor-κB activation:: common genetic etiology with Blau syndrome
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DOI：
10.1182/blood-2004-07-2972
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发表时间：
2005-02-01
期刊：
影响因子：
20.3
通讯作者：
Miyachi, Y
中科院分区：
文献类型：
--
作者：
Kanazawa, N;Okafuji, I;Miyachi, Y
早发性结节病(EOS)和遗传性Blau综合征(BS)具有幼年型系统性肉芽肿综合征的典型临床特征，主要影响皮肤、关节和眼睛。然而，没有直接证据表明这两种疾病可能是共同的起源。最近在BS家族中发现的CARD15突变促使我们研究EOS患者中类似的CARD15突变。在日本收集的10例EOS病例中，9例发现杂合性错义突变；4例在BS中发现1000C>；T(氨基酸改变中的R334W)，4例发现新的1487A>；T(H496L)、1538T>；C(M513T)、1813A>；C(T605P)和2010C>；A(N670K)，1例在不同等位基因上发现1146C>；G(D382E)/1834G>；A(A612T)双重突变。CARD15的6个变异体均表现出基础核因子-kappaB活性增强。这些发现表明，大多数EOS和BS病例都有共同的CARD15突变的遗传病因，这些突变导致结构性的NF-kappaB激活。(C)2005年，由美国血液病学会提供。
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. (C) 2005 by The American Society of Hematology.