P67-phox (NCF2) Lacking Exons 11 and 12 Is Functionally Active and Leads to an Extremely Late Diagnosis of Chronic Granulomatous Disease (CGD)
P67-phox (NCF2) Lacking Exons 11 and 12 Is Functionally Active and Leads to an Extremely Late Diagnosis of Chronic Granulomatous Disease (CGD)
复制标题
缺乏外显子 11 和 12 的 P67-phox (NCF2) 功能活跃，导致慢性肉芽肿病 (CGD) 的诊断极晚
作者：
J. Roesler;F. Segerer;H. Morbach;S. Kleinert;S. Thieme;A. Rösen‐Wolff;J. Liese
两名五十多岁的兄弟分别有疑似真菌过敏、过敏性支气管肺曲霉病、肺泡炎以及侵袭性曲霉病和肺瘘的病史。最终，在拖延了 50 年之后，指标患者被诊断出患有慢性肉芽肿病 (CGD)。我们在 NCF2 (p67-phox) 基因 c.1000+2T→G 中发现了一个新的剪接突变，该突变导致了几种剪接产物，其中之一缺少外显子 11 和 12。这种缺失符合读码框，并通过使用逆转录病毒载体的转导实验测定，具有显着的残留 NADPH 氧化酶活性。我们得出结论，缺乏两个外显子编码的 34 个氨基酸的 p67-phox 仍然可以发挥相当大的功能活性。这项活动可以部分解释患者在没有充分诊断和治疗的情况下能够长期生存，但无法阻止进行性肺损伤。
Two brothers in their fifties presented with a medical history of suspected fungal allergy, allergic bronchopulmonary aspergillosis, alveolitis, and invasive aspergillosis and pulmonary fistula, respectively. Eventually, after a delay of 50 years, chronic granulomatous disease (CGD) was diagnosed in the index patient. We found a new splice mutation in the NCF2 (p67-phox) gene, c.1000+2T→G, that led to several splice products one of which lacked exons 11 and 12. This deletion was in frame and allowed for remarkable residual NADPH oxidase activity as determined by transduction experiments using a retroviral vector. We conclude that p67-phox which lacks the 34 amino acids encoded by the two exons can still exert considerable functional activity. This activity can partially explain the long-term survival of the patients without adequate diagnosis and treatment, but could not prevent progressing lung damage.
登录
查看更多内容
DOI：
10.1056/nejmoa1007097
发表时间：
2010-12-30
期刊：
The New England journal of medicine
影响因子：
--
作者：
Kuhns DB;Alvord WG;Heller T;Feld JJ;Pike KM;Marciano BE;Uzel G;DeRavin SS;Priel DA;Soule BP;Zarember KA;Malech HL;Holland SM;Gallin JI
通讯作者：
Gallin JI
一名 69 岁男性患有慢性肉芽肿病。
DOI：
10.1056/nejm199112193252506
发表时间：
1991
期刊：
The New England journal of medicine
影响因子：
--
作者：
Schapiro,BL;Newburger,PE;Klempner,MS;Dinauer,MC
通讯作者：
Dinauer,MC
影响因子：
2.3
作者：
Roos, Dirk;Kuhns, Douglas B.;Maddalena, Anne;Roesler, Joachim;Alvaro Lopez, Juan;Ariga, Tadashi;Avcin, Tadej;de Boer, Martin;Bustamante, Jacinta;Condino-Neto, Antonio;Di Matteo, Gigliola;He, Jianxin;Hill, Harry R.;Holland, Steven M.;Kannengiesser, Caroline;Koker, M. Yavuz;Kondratenko, Irina;van Leeuwen, Karin;Malech, Harry L.;Marodi, Laszlo;Nunoi, Hiroyuki;Stasia, Marie-Jose;Ventura, Anna Maria;Witwer, Carl T.;Wolach, Baruch;Gallin, John I.
通讯作者：
Gallin, John I.
DOI：
10.1016/j.bcmd.2010.01.009
发表时间：
2010-04-15
期刊：
Blood cells, molecules & diseases
影响因子：
--
作者：
Roos D;Kuhns DB;Maddalena A;Bustamante J;Kannengiesser C;de Boer M;van Leeuwen K;Köker MY;Wolach B;Roesler J;Malech HL;Holland SM;Gallin JI;Stasia MJ
通讯作者：
Stasia MJ
DOI：
10.1073/pnas.080074897
发表时间：
2000-04-25
影响因子：
11.1
作者：
Ambruso, DR;Knall, C;Roos, D
通讯作者：
Roos, D