Genetic and functional analysis of two missense mutations in CD46 predispose to postpartum atypical hemolytic uremic syndrome.
Genetic and functional analysis of two missense mutations in CD46 predispose to postpartum atypical hemolytic uremic syndrome.
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CD46 中两个错义突变的遗传和功能分析易导致产后非典型溶血性尿毒症综合征。
DOI：
10.1016/j.cca.2020.01.009
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发表时间：
2020-01
影响因子：
5
通讯作者：
Zhao Ming-Hui
中科院分区：
文献类型：
--
作者：
Wu Hao;Mao Zhaomin;Tan Ying;Jiang Yanfang;Yu Jinyu;Song Li;Wu Shan;Sun Mindan;Zhu Li;Yu Xiaojuan;Zhang Li;Yu Feng;Zhao Ming-Hui
Pregnancy associated atypical hemolytic uremic syndrome (p-aHUS) is a disease with a triad of hemolytic anemia, thrombocytopenia and acute renal failure, which might be attributed to the uncontrolled complement activation. Herein, we sequenced a postpartum-aHUS patient and found the two missense variants of CD46, a novel mutation (c.403G > C, p.G135R) from her father and a once reported mutation (c.293C > T, p.T98I) without expressional and functional tests from her mother. The G135R mutation caused a significantly reduced membrane expression of CD46 in peripheral blood lymphocyte and renal cells. The T98I mutation caused a mild decrease membrane expression of CD46 in peripheral blood lymphocyte cells. Moreover, the expressed G135R protein was in precursor form, indicating that this mutant was retained intracellularly. The C3b binding ability of T98I mutant was slightly decreased while the C4b binding ability is not significantly changed. The cofactor ability of the two mutants for factor I in the degradation of C3b was demonstrated to be impaired. This study reported the first case of a four-generation postpartum-aHUS pedigree with isolated CD46 variants and the detailed disease progression, treatment, and prognosis provided more meaningful information for the understanding the disease.
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DOI：
10.1084/jem.175.6.1547
发表时间：
1992-06-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Oglesby TJ;Allen CJ;Liszewski MK;White DJ;Atkinson JP
通讯作者：
Atkinson JP
DOI：
--
发表时间：
--
期刊：
--
影响因子：
--
作者：
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通讯作者：
E. Demir;H. Yazıcı;Y. Ozluk;I. Kílícaslan;A. Turkmen
影响因子：
3
作者：
Bhatia, Divya;Khandelwal, Priyanka;Bagga, Arvind
通讯作者：
Bagga, Arvind
DOI：
10.1016/j.cca.2019.03.1623
发表时间：
2019-07
期刊：
Clinica chimica acta; international journal of clinical chemistry
影响因子：
--
作者：
Min-Hua Tseng;J. Tsai;I. Tsai;Shih-Ming Huang;Jing-Long Huang;W. Fan;Hwei-Jen Lee;Tai-Wei Wu;Shih-Hua Lin
通讯作者：
Min-Hua Tseng;J. Tsai;I. Tsai;Shih-Ming Huang;Jing-Long Huang;W. Fan;Hwei-Jen Lee;Tai-Wei Wu;Shih-Hua Lin
影响因子：
4.4
作者：
E. Adams;M. Brown;M. Nunge;M. Krych;J. Atkinson
通讯作者：
E. Adams;M. Brown;M. Nunge;M. Krych;J. Atkinson