| Item type |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2021-08-20 |
| タイトル |
|
|
タイトル |
Identification of a deep intronic POLR3A variant causing inclusion of a pseudo-exon derived from an Alu element in Pol III-related leukodystrophy |
|
言語 |
en |
| 言語 |
|
|
言語 |
eng |
| キーワード |
|
|
主題 |
Deep intronic variants |
| キーワード |
|
|
主題 |
Pseudo-exon inclusion |
| キーワード |
|
|
主題 |
POLR3A |
| キーワード |
|
|
主題 |
whole-genome sequencing |
| キーワード |
|
|
主題 |
SpliceAI |
| 資源タイプ |
|
|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| その他のタイトル |
|
|
その他のタイトル |
A deep intronic variant in POLR3A |
| 著者 |
Hiraide, Takuya
Nakashima, Mitsuko
Ikeda, Takahiro
Tanaka, Daisuke
Osaka, Hitoshi
Saitsu, Hirotomo
|
| 書誌情報 |
Journal of human genetics
巻 65,
号 10,
p. 921-925,
発行日 2020-10
|
| 出版者 |
|
|
出版者 |
Springer Nature |
| 権利 |
|
|
権利情報 |
"This is a post-peer-review, pre-copyedit version of an article published in ""Journal of human genetics"". The final authenticated version is available online at: https://doi.org/10.1038/s10038-020-0786-y." |
| 抄録 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
Pseudo-exon inclusion caused by deep intronic variants is an important genetic cause for various disorders. Here, we present a case of a hypomyelinating leukodystrophy with developmental delay, intellectual disability, autism spectrum disorder and hypodontia, which are consistent with autosomal recessive POLR3-related leukodystrophy. Whole-exome sequencing identified only a heterozygous missense variant (c.1451G>A) in POLR3A. To explore possible involvement of a deep intronic variant in another allele, we performed whole-genome sequencing of the patient with variant annotation by SpliceAI, a deep learning-based splicing prediction tool. A deep intronic variant (c.645+312C>T) in POLR3A, which was predicted to cause inclusion of a pseudo-exon derived from an Alu element, was identified and confirmed by mRNA analysis. These results clearly showed that whole-genome sequencing, in combination with deep-learning based annotation tools such as SpliceAI, will bring us further benefits in detecting and evaluating possible pathogenic variants in deep intronic regions. |
| ISSN |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
1434-5161 |
| EISSN |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
1435-232X |
| PubMed番号 |
|
|
関連タイプ |
isVersionOf |
|
|
識別子タイプ |
PMID |
|
|
関連識別子 |
32483275 |
| 出版社DOI |
|
|
関連タイプ |
isVersionOf |
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
10.1038/s10038-020-0786-y |
| 著者版フラグ |
|
|
出版タイプ |
AM |
|
出版タイプResource |
http://purl.org/coar/version/c_ab4af688f83e57aa |
JHG-65-921.pdf (1.4 MB)
