一种新型供体位点通过 CFTR mRNA 分析导致 CF 患者出现新的假外显子。

A novel donor splice site characterized by CFTR mRNA analysis induces a new pseudo-exon in CF patients.

机构信息

Medical Genetics Laboratory, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Commenda, 12, 20122 Milan, Italy.

出版信息

J Cyst Fibros. 2010 Dec;9(6):411-8. doi: 10.1016/j.jcf.2010.08.009. Epub 2010 Sep 26.

DOI:10.1016/j.jcf.2010.08.009

PMID:20875776

Abstract

BACKGROUND

The CFTR gene is tightly regulated and differentially expressed in many mucosal epithelial cell types. There is evidence of an increasing number of genomic variations in the intronic regions influencing mRNA splicing, and also the level of normal CFTR transcript.

METHODS

In the present study, we investigate the molecular defect by RT-PCR analyzing the mRNA of 25 cystic fibrosis (CF) patients in whom only one or no CF allele had been identified after DNA analysis (of all the exons of the CFTR gene).

RESULTS

mRNA analysis led to the detection of a cryptic exon in two patients: the new exon is a 104 bp insertion between exons 10 and 11 and is caused by a new point mutation c.1584+18672 bp A>G (http://www.hgvs.org/mutnomen/) discovered in intron 10; moreover, they showed the absence of exon 9 skipping.

CONCLUSIONS

Our results confirm the utility of RNA analysis in discovering new mutations and in investigating their effect on normal splicing processes.

摘要

背景

CFTR 基因在许多黏膜上皮细胞类型中受到严格调控和差异表达。有证据表明，越来越多的基因组变异存在于影响 mRNA 剪接的内含子区域，以及正常 CFTR 转录本的水平。

方法

在本研究中，我们通过 RT-PCR 分析了 25 名囊性纤维化 (CF) 患者的 mRNA，这些患者在 DNA 分析后仅发现一个或没有 CF 等位基因 (CFTR 基因的所有外显子)。

结果

mRNA 分析导致在两名患者中检测到一个隐匿外显子：新外显子是在第 10 号和第 11 号外显子之间插入的 104bp，由第 10 号内含子中新的点突变 c.1584+18672 bp A>G (http://www.hgvs.org/mutnomen/)引起；此外，他们还显示 9 号外显子跳跃缺失。