Analysis of class switch recombination and somatic hypermutation in patients affected with autosomal dominant hyper-IgM syndrome type 2
Analysis of class switch recombination and somatic hypermutation in patients affected with autosomal dominant hyper-IgM syndrome type 2
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DOI：
10.1016/j.clim.2005.02.003
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发表时间：
2005-06-01
影响因子：
8.6
通讯作者：
Durandy, A
中科院分区：
文献类型：
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作者：
Imai, K;Zhu, Y;Durandy, A
高IgM综合征2型常染色体隐性遗传型（AR-HIGM 2）是继发于AICDA基因编码激活诱导的胞苷脱氨酶的两个等位基因的突变，其特征在于大多数患者的免疫球蛋白类别转换重组（CSR）和体细胞高突变（SHM）缺陷。我们在此报告了7例携带AICDA单杂合R190 X突变的患者的免疫表型。体内CSR中的可变缺陷作为常染色体显性（AD）性状遗传，强烈表明这种杂合AICDA突变导致HIGH M（AD-HIGH M2）。在AD-HIGH M2 B细胞中，CSR在体外一直被发现受损。与AR-HIGM 2相比，CSR诱导的IgM重链基因开关区双链DNA断裂有9例。B细胞IgM重链基因V区SHM频率除1例外均正常。AD-HIGM 2表型的特征性研究表明，AID C-末端区域可能参与CSR所需的DNA修复机制。(c)2005年爱思唯尔公司All rights reserved.
Autosomal recessive form of hyper-IgM syndrome type 2 (AR-HIGM2) is secondary to mutations affecting both alleles of AICDA gene encoding activation-induced cytidine deaminase, characterized by defects of immunoglobulin class switch recombination (CSR) and somatic hypermutation (SHM) in most of the patients. We herein report the immunological phenotype of seven patients carrying a single heterozygous R190X mutation in AICDA. Variable defect in in vivo CSR inherited as an autosomal dominant (AD) trait strongly suggests that this heterozygous AICDA mutation causes HIGM (AD-HIGM2). In AD-HIGM2 B cells, CSR was consistently found impaired in vitro. However, in contrast to AR-HIGM2, the CSR-induced double-stranded DNA breaks in the switch region of IgM heavy chain gene were 9 detected. The SHM frequency in V regions of IgM heavy chain gene in B cells was normal in all (but one patient). The characteristics sties of the AD-HIGM2 phenotype indicate that the AID C-terminal region may be involved in DNA repair machinery required for CSR. (c) 2005 Elsevier Inc. All rights reserved.