• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

基于迷你基因的剪接分析为 PKHD1 基因内含子变异提供了新的见解。

Minigene-based splice assays provide new insights on intronic variants of the PKHD1 gene.

机构信息

Department of Nephrology, The Affiliated Municipal Hospital of Qingdao University, No.5 Donghai Middle Road, Qingdao, 266071, China.

School of Clinical Medicine, Shandong Second Medical University, Weifang, 261000, China.

出版信息

Hum Genomics. 2024 Nov 9;18(1):122. doi: 10.1186/s40246-024-00675-9.

DOI:10.1186/s40246-024-00675-9
PMID:39521997
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11550526/
Abstract

BACKGROUND

Autosomal Recessive Polycystic Kidney Disease (ARPKD) is a rare hereditary disorder caused by variants in PKHD1. Currently, aberrant splicing has been reported to play important roles in genetic disease. Our goal is to analyze intronic variants in PKHD1 at the mRNA level.

RESULTS

The 12 candidate variants were introduced into the corresponding minigene and functionally assayed in HEK 293T and Hela cells. We identified 11 variants that induce splicing alterations, resulting in various consequences such as skipping of exons, intron retention and protein truncation.

CONCLUSIONS

This underlined the importance of mRNA-level assessment for genetic diagnostics in related genetic disorders.

摘要

背景

常染色体隐性多囊肾病 (ARPKD) 是一种由 PKHD1 变异引起的罕见遗传性疾病。目前，异常剪接已被报道在遗传疾病中发挥重要作用。我们的目标是在 mRNA 水平上分析 PKHD1 的内含子变异。

结果

将 12 个候选变体引入相应的小基因，并在 HEK 293T 和 Hela 细胞中进行功能测定。我们鉴定出 11 个变体可诱导剪接改变，导致外显子跳跃、内含子保留和蛋白质截断等各种后果。

结论

这强调了在相关遗传疾病的遗传诊断中进行 mRNA 水平评估的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a06f/11550526/e6354858bcb5/40246_2024_675_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a06f/11550526/e6354858bcb5/40246_2024_675_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a06f/11550526/e6354858bcb5/40246_2024_675_Fig1_HTML.jpg

相似文献

1
Minigene-based splice assays provide new insights on intronic variants of the PKHD1 gene.基于迷你基因的剪接分析为 PKHD1 基因内含子变异提供了新的见解。
Hum Genomics. 2024 Nov 9;18(1):122. doi: 10.1186/s40246-024-00675-9.
2
A rare deep intronic mutation of PKHD1 gene, c.8798-459 C > A, causes autosomal recessive polycystic kidney disease by pseudoexon activation.PKHD1 基因的一个罕见深内含子突变，c.8798-459 C > A，通过假外显子激活导致常染色体隐性多囊肾病。
J Hum Genet. 2019 Mar;64(3):207-214. doi: 10.1038/s10038-018-0550-8. Epub 2019 Jan 7.
3
A novel splicing variant identified in a fetus with autosomal recessive polycystic kidney disease.在一名患有常染色体隐性多囊肾病的胎儿中鉴定出一种新型剪接变体。
Front Genet. 2023 Jun 29;14:1207772. doi: 10.3389/fgene.2023.1207772. eCollection 2023.
4
A Deep Intronic PKHD1 Variant Identified by SpliceAI in a Deceased Neonate With Autosomal Recessive Polycystic Kidney Disease.SpliceAI 鉴定的常染色体隐性多囊肾病死亡新生儿中的深度内含子 PKHD1 变异。
Am J Kidney Dis. 2024 Jun;83(6):829-833. doi: 10.1053/j.ajkd.2023.12.011. Epub 2024 Jan 10.
5
Intragenic motifs regulate the transcriptional complexity of Pkhd1/PKHD1.基因内基序调控Pkhd1/PKHD1的转录复杂性。
J Mol Med (Berl). 2014 Oct;92(10):1045-56. doi: 10.1007/s00109-014-1185-7. Epub 2014 Jul 3.
6
Functional analysis of PKHD1 splicing in autosomal recessive polycystic kidney disease.常染色体隐性多囊肾病中PKHD1剪接的功能分析
J Hum Genet. 2006;51(9):788-793. doi: 10.1007/s10038-006-0022-4. Epub 2006 Aug 3.
7
PKHD1 gene silencing may cause cell abnormal proliferation through modulation of intracellular calcium in autosomal recessive polycystic kidney disease.在常染色体隐性多囊肾病中，PKHD1基因沉默可能通过调节细胞内钙水平导致细胞异常增殖。
J Biochem Mol Biol. 2007 Jul 31;40(4):467-74. doi: 10.5483/bmbrep.2007.40.4.467.
8
Pseudoexon activation in the PKHD1 gene: a French founder intronic mutation IVS46+653A>G causing severe autosomal recessive polycystic kidney disease.PKHD1基因中的假外显子激活：一种导致严重常染色体隐性多囊肾病的法国奠基者内含子突变IVS46+653A>G
Clin Genet. 2009 Feb;75(2):203-6. doi: 10.1111/j.1399-0004.2008.01106.x. Epub 2008 Nov 17.
9
Molecular genetic analysis of PKHD1 by next-generation sequencing in Czech families with autosomal recessive polycystic kidney disease.在捷克常染色体隐性多囊肾病家庭中通过新一代测序对PKHD1进行分子遗传学分析。
BMC Med Genet. 2015 Dec 22;16:116. doi: 10.1186/s12881-015-0261-3.
10
Challenges in establishing genotype-phenotype correlations in ARPKD: case report on a toddler with two severe PKHD1 mutations.常染色体隐性多囊肾病中建立基因型-表型相关性的挑战：一名患有两种严重PKHD1突变幼儿的病例报告
Pediatr Nephrol. 2017 Jul;32(7):1269-1273. doi: 10.1007/s00467-017-3648-x. Epub 2017 Mar 31.

本文引用的文献

1
The molecular structure and function of fibrocystin, the key gene product implicated in autosomal recessive polycystic kidney disease (ARPKD).纤毛病相关蛋白的分子结构和功能，该蛋白是常染色体隐性多囊肾病（ARPKD）相关的关键基因产物。
Ann Hum Genet. 2024 Jan;88(1):58-75. doi: 10.1111/ahg.12535. Epub 2023 Oct 31.
2
Fibrocystin/Polyductin releases a C-terminal fragment that translocates into mitochondria and suppresses cystogenesis.纤维囊蛋白/多囊蛋白释放一个 C 末端片段，该片段易位进入线粒体并抑制囊泡生成。
Nat Commun. 2023 Oct 16;14(1):6513. doi: 10.1038/s41467-023-42196-4.
3
Identified eleven exon variants in PKD1 and PKD2 genes that altered RNA splicing by minigene assay.
鉴定了 PKD1 和 PKD2 基因中的 11 个外显子变异，通过小基因检测证实这些变异改变了 RNA 的剪接。
BMC Genomics. 2023 Jul 19;24(1):407. doi: 10.1186/s12864-023-09444-9.
4
A Potential Therapy Using Antisense Oligonucleotides to Treat Autosomal Recessive Polycystic Kidney Disease.一种使用反义寡核苷酸治疗常染色体隐性多囊肾病的潜在疗法。
J Clin Med. 2023 Feb 10;12(4):1428. doi: 10.3390/jcm12041428.
5
Regulation of pre-mRNA splicing: roles in physiology and disease, and therapeutic prospects.前体mRNA剪接的调控：在生理和疾病中的作用以及治疗前景。
Nat Rev Genet. 2023 Apr;24(4):251-269. doi: 10.1038/s41576-022-00556-8. Epub 2022 Dec 16.
6
Clinical features of autosomal recessive polycystic kidney disease in the Japanese population and analysis of splicing in PKHD1 gene for determination of phenotypes.日本人常染色体隐性多囊肾病的临床特征及 PKHD1 基因剪接分析对表型的影响。
Clin Exp Nephrol. 2022 Feb;26(2):140-153. doi: 10.1007/s10157-021-02135-3. Epub 2021 Sep 18.
7
Possible PKHD1 Hot-spot Mutations Related to Early Kidney Function Failure or Hepatofibrosis in Chinese Children with ARPKD: A Retrospective Single Center Cohort Study and Literature Review.可能与中国人 ARPKD 患儿早期肾功能衰竭或肝纤维化相关的 PKHD1 热点突变：一项回顾性单中心队列研究和文献复习。
Curr Med Sci. 2020 Oct;40(5):835-844. doi: 10.1007/s11596-020-2268-z. Epub 2020 Oct 29.
8
Multiplexed CRISPR/Cas9-mediated knockout of 19 Fanconi anemia pathway genes in zebrafish revealed their roles in growth, sexual development and fertility.多重 CRISPR/Cas9 介导的斑马鱼 19 个范可尼贫血通路基因敲除揭示了它们在生长、性发育和生育中的作用。
PLoS Genet. 2018 Dec 12;14(12):e1007821. doi: 10.1371/journal.pgen.1007821. eCollection 2018 Dec.
9
Splicing mutations in human genetic disorders: examples, detection, and confirmation.人类遗传疾病中的剪接突变：实例、检测与确认
J Appl Genet. 2018 Aug;59(3):253-268. doi: 10.1007/s13353-018-0444-7. Epub 2018 Apr 21.
10
Polycystic kidney disease.多囊肾病
N Engl J Med. 2004 Jan 8;350(2):151-64. doi: 10.1056/NEJMra022161.