An Explanation for the Phenotypic Differences between Patients Bearing Partial Deletions of the DMD Locus
An Explanation for the Phenotypic Differences between Patients Bearing Partial Deletions of the DMD Locus
复制标题
DOI：
10.1016/0888-7543(88)90113-9
复制
发表时间：
1988-01-01
期刊：
影响因子：
4.4
通讯作者：
Kunkel, Louis M.
中科院分区：
文献类型：
--
作者：
Monaco, Anthony P.;Bertelson, Corlee J.;Kunkel, Louis M.
缺失导致杜氏肌营养不良症（DMD）和不太严重的贝克尔肌营养不良症（BMD）发生在人类X染色体短臂上的同一个大基因中。我们提出了一种分子机制来解释DMD和BMD患者之间的严重程度的临床差异承担相同的基因位点的部分缺失。该模型基于基因内缺失的断点及其对三联体密码子翻译成蛋白质产物的氨基酸的影响。在三名DMD患者中鉴定的缺失显示出移位三联体密码子的氨基酸的翻译开放阅读框（ORF），并且预测每个缺失导致截短的异常蛋白质产物。在三个BMD患者中鉴定的缺失显示维持氨基酸的翻译ORF，并预测较短、较低分子量的蛋白质。较小的蛋白质产物被认为是半功能性的，并导致较温和的临床表型。相同的ORF机制也适用于潜在的5'和3'内含子剪接突变及其对蛋白质产生和临床表型的影响。(C)1988年出版社出版。
Deletions giving rise to Duchenne muscular dystrophy (DMD) and the less severe Becker muscular dystrophy (BMD) occur in the same large gene on the short arm of the human X chromosome. We present a molecular mechanism to explain the clinical difference in severity between DMD and BMD patients who bear partial deletions of the same gene locus. The model is based on the breakpoints of intragenic deletions and their effect on the translation of triplet codons into amino acids of the protein product. Deletions identified in three DMD patients are shown to shift the translational open reading frame (ORF) of triplet codons for amino acids, and each deletion is predicted to result in a truncated, abnormal protein product. Deletions identified in three BMD patients are shown to maintain the translational ORF for amino acids and predict a shorter, lower molecular weight protein. The smaller protein product is presumed to be semifunctional and to result in a milder clinical phenotype. The same ORF mechanism is also applicable to potential 5' and 3' intron splice mutations and their effect on protein production and clinical phenotype. (C) 1988 Academic Press, Inc.