2015 Fiscal Year Final Research Report
Identification of novel pathogenic genes for congenital hemolytic anemia and establishment of comprehensive gene testing
| Project/Area Number |
25461609
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
KANNO HITOSHI 東京女子医科大学, 医学部, 教授 (70221207)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Keywords | 溶血性貧血 / 赤血球膜 / リン脂質 / 貪食目印分子 / 単一遺伝子病 |
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| Outline of Final Research Achievements |
We analyzed 50 cases of congenital hemolytic anemia (CHA) by the whole exome sequencing, and identified that a male patient had a nonsynonymous SNV in ATP11C on the X chromosome, c.1253C>A, corresponding to p.Thr418Asn. The proband was hemizygous and the mother was heterozygous for this mutation, as determined by direct sequencing.Thr418 is located near Asp412, the phosphorylation site for the active transport of phosphatidylserine(PS). Flipping activity was measured by monitoring PS internalization using flow cytometry, and the patient's red cells showed dramatically decreased flippase activity. Because red cells with exposed PS can be phagocytosed through recognition as eat-me signals, ATP11C deficiency presumably causes extra-vascular hemolysis.
The comprehensive gene tests enable us to make a correct differential diagnosis of CHA, and we showed that they are particularly useful to avoid serious complications such as venous thrombosis after splenectomy in PIEZO1 deficiency.
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| Free Research Field |
医歯薬学
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