論文 - 詳細
| RRC ID | 36730 |
|---|---|
| 著者 | Yokoi S, Ishihara N, Miya F, Tsutsumi M, Yanagihara I, Fujita N, Yamamoto H, Kato M, Okamoto N, Tsunoda T, Yamasaki M, Kanemura Y, Kosaki K, Kojima S, Saitoh S, Kurahashi H, Natsume J. |
| タイトル | TUBA1A mutation can cause a hydranencephaly-like severe form of cortical dysgenesis. |
| ジャーナル | Sci Rep |
| Abstract |
TUBA1A mutations cause a wide spectrum of lissencephaly and brain malformations. Here, we report two patients with severe cortical dysgeneses, one with an extremely thin cerebral parenchyma apparently looking like hydranencephaly and the other with lissencephaly accompanied by marked hydrocephalus, both harbouring novel de novo missense mutations of TUBA1A. To elucidate how the various TUBA1A mutations affect the severity of the phenotype, we examined the capacity of the mutant protein to incorporate into the endogenous microtubule network in transfected COS7 cells by measuring line density using line extraction in an immunofluorescence study. The mutants responsible for severe phenotypes were found to incorporate extensively into the network. To determine how each mutant alters the microtubule stability, we examined cold-induced microtubule depolymerisation in fibroblasts. The depolymerisation of patients' fibroblasts occurred earlier than that of control fibroblasts, suggesting that microtubules bearing mutated tubulins are unstable. Both mutations are predicted to participate in lateral interactions of microtubules. Our data suggest that the TUBA1A mutations disrupting lateral interactions have pronounced dominant-negative effects on microtubule dynamics that are associated with the severe end of the lissencephaly spectrum. |
| 巻・号 | 5 |
| ページ | 15165 |
| 公開日 | 2015-10-23 |
| DOI | 10.1038/srep15165 |
| PII | srep15165 |
| PMID | 26493046 |
| PMC | PMC4615979 |
| MeSH | Child, Preschool Exome Female Humans Hydranencephaly / genetics* Male Malformations of Cortical Development / genetics* Mutation* Sequence Analysis Tubulin / genetics* |
| IF | 3.998 |
| 引用数 | 10 |
| WOS 分野 | GENETICS & HEREDITY |
| 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 | 2 |
| 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 | |
| 遺伝子材料 | pCMV-TUBA1A flag-WT (RDB14140) pCMV-TUBA1A flag-R64W (RDB14141) pCMV-TUBA1A flag-C25F (RDB14142) pCMV-TUBA1A flag-R402C (RDB14143) pCMV-TUBA1A myc-WT (RDB14144) pCMV-TUBA1A myc-R64W (RDB14145) pCMV-TUBA1A myc- C25F (RDB14146) pCMV-TUBA1A myc- R402C (RDB14147). |