| Title: | Moyamoya Disease Associated with a Deficiency of Complement Component 6 |
| Authors: | Kato, Masaru Browse this author →KAKEN DB |
| Kudo, Yuki Browse this author |
| Hatase, Masanao Browse this author |
| Tsuchida, Naohisa Browse this author |
| Takeyama, Shuhei Browse this author |
| Sugiyama, Taku Browse this author |
| Fujimura, Miki Browse this author |
| Yabe, Ichiro Browse this author |
| Tsujimoto, Hiroshi Browse this author |
| Fukumori, Yasuo Browse this author |
| Inoue, Norimitsu Browse this author |
| Atsumi, Tatsuya Browse this author →KAKEN DB |
| Keywords: | Complement |
| Complement component 6 |
| C6 gene |
| Homozygous mutation |
| Complement deficiency |
| Moyamoya disease |
| Issue Date: | Aug-2022 |
| Publisher: | Elsevier |
| Journal Title: | Journal of Stroke and Cerebrovascular Diseases |
| Volume: | 31 |
| Issue: | 8 |
| Start Page: | 106601 |
| Publisher DOI: | 10.1016/j.jstrokecerebrovasdis.2022.106601 |
| Abstract: | Objectives: Complement component 6 (C6) deficiency is a very rare genetic defect that leads to significantly diminished synthesis, secretion, or function of C6. In the current report, we demonstrate a previously undescribed, homozygous missense mutation in exon 17 of the C6 gene (c.2545A>G p.Arg849Gly) in a 35-year-old Japanese woman with moyamoya disease and extremely low levels of CH50 (<7.0 U/mL).
Materials and Methods: The complement gene analysis using hybridization capture-based next generation sequencing was performed. CH50 was determined in patient's plasma mixed with plasma from a healthy donor or purified human C6 protein. Western blot was performed on patient's plasma using polyclonal antibodies against C6, with healthy donor's plasma and purified human C6 protein as positive controls while C6-depleted human serum as a negative control. The carriage of ring finger protein 213 variant (c.14576G>A p.Arg4859Lys), a susceptibility gene for moyamoya disease, was examined by direct sequencing.
Results: CH50 mixing test clearly showed a deficiency pattern, being rescued by addition of only 1% healthy donor's plasma or 1 μg/mL purified human C6 protein (1/50-1/100 of physiological concentration). Western blot revealed the absence of C6 protein in the patient's plasma, confirming a quantitative deficiency of C6. The ring finger protein 213 variant was not detected.
Conclusions: Our data implies that unrecognized complement deficiencies would be harbored in cerebrovascular diseases with unknown etiologies. |
| Rights: | © 2022. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/90394 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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