論文 - 詳細
| RRC ID | 77249 |
|---|---|
| 著者 | Zhang Y, Xie H, Liang G, Qin Y, Wei X, Ning S, Liang Y, Liang X, Xie Y, Lin Z, Zhu D, Lin J, Xiong F, Xu X, Shang X. |
| タイトル | A novel gain-of-function PIP4K2A mutation elevates the expression of β-globin and aggravates the severity of α-thalassemia. |
| ジャーナル | Br J Haematol |
| Abstract |
Haemoglobin H (Hb H) disease (intermediate status of α-thalassemia) shows marked phenotypic variability from asymptomatic to severe anaemia. Apart from the combined β-thalassemia allele ameliorating clinical severity, reports of genetic modifier genes affecting the phenotype of Hb H disease are scarce which bring inconvenience to precise diagnosis and genetic counselling of the patients. Here, we present a novel mutation (c.948C>A, p.S316R) in the PIP4K2A gene in a female Hb H disease patient who displayed moderate anaemia and a relatively high Hb H level. Haematological analysis in her family members revealed that individuals carrying this mutation have upregulated β-globin expression, leading to a more imbalanced β/α-globin ratio and more Hb H inclusion bodies in peripheral red blood cells. According to functional experiments, the mutant PIP4K2A protein exhibits enhanced protein stability, increased kinase activity and a stronger regulatory effect on downstream proteins, suggesting a gain-of-function mutation. Moreover, introduction of the S316R mutation into HUDEP-2 cells increased expression of β-globin, further inhibiting erythroid differentiation and terminal enucleation. Thus, the S316R mutation is a novel genetic factor associated with β-globin expression, and the PIP4K2A gene is a new potential modifier gene affecting the α-thalassemia phenotype. |
| 巻・号 | 202(5) |
| ページ | 1018-1023 |
| 公開日 | 2023-9-1 |
| DOI | 10.1111/bjh.18967 |
| PMID | 37423903 |
| MeSH | Female Gain of Function Mutation Humans Mutation Phenotype Phosphotransferases (Alcohol Group Acceptor) / genetics alpha-Thalassemia* / genetics beta-Globins / genetics beta-Thalassemia* / genetics |
| IF | 5.518 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 18 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | HUDEP-2(RCB4557) |