Bartolo C, Papp A C, Snyder P J, Sedra M S, Burghes A H, Hall C D, Mendell J R, Prior T W
Department of Molecular Genetics, Ohio State University, Columbus 43210, USA.
J Med Genet. 1996 Apr;33(4):324-7. doi: 10.1136/jmg.33.4.324.
A Becker muscular dystrophy patient was found to have a single base substitution at the 5' end of intron 54. This single base substitution disrupts the invariant GT dinucleotide within the 5' donor splice site and was shown to cause an out of frame deletion of exon 54 during mRNA processing. This is predicted to produce a truncated dystrophin protein which is more consistent with a DMD phenotype. However, small quantities of normal mRNA are also transcribed and these are sufficient to produce a reduced amount of normal molecular weight dystrophin and give rise to a milder BMD phenotype. This indicates that a single base substitution at an invariant dinucleotide of the splice site consensus sequence may still allow read through of the message and allow the production of some normal protein. This shows that there are a greater number of possible intronic mutations that can lead to a mild phenotype and it also underlines the importance of performing cDNA analysis when screening for small gene alterations in the BMD patient population.
一名贝克型肌营养不良患者被发现在内含子54的5'端存在一个单碱基替换。这个单碱基替换破坏了5'供体剪接位点内不变的GT二核苷酸，并在mRNA加工过程中导致外显子54的框外缺失。预计这会产生一种截短的抗肌萎缩蛋白，这与杜氏肌营养不良症（DMD）的表型更为一致。然而，也转录了少量正常mRNA，这些足以产生数量减少的正常分子量抗肌萎缩蛋白，并导致较轻的贝克型肌营养不良症（BMD）表型。这表明剪接位点共有序列不变二核苷酸处的单碱基替换仍可能允许通读信息并允许产生一些正常蛋白质。这表明有更多可能的内含子突变可导致轻度表型，这也强调了在筛查BMD患者群体中的小基因改变时进行cDNA分析的重要性。
