Identification of mutations in two major mRNA isoforms of the Chediak-Higashi syndrome gene in human and mouse
Identification of mutations in two major mRNA isoforms of the Chediak-Higashi syndrome gene in human and mouse
复制标题
DOI：
10.1093/hmg/6.7.1091
复制
发表时间：
1997-07-01
影响因子：
3.5
通讯作者：
Kingsmore, SF
中科院分区：
文献类型：
--
作者：
Barbosa, MDFS;Barrat, FJ;Kingsmore, SF
Chediak-Higashi综合征是一种常染色体隐性遗传的免疫缺陷病，主要表现为细胞内蛋白质转运异常。这些同种型在其编码结构域的3'端的大小和序列上都不同，较小的同种型（类似于5.8 kb）由不完全剪接和通过内含子的阅读产生。这些mRNA在转录的组织分布和预测的生物学特性方面也不同。在三名CHS患者中，在两种亚型共有的编码结构域区域内鉴定了新突变：产生终止密码子的C-->T转换（R50 X和Q1029 X），并发现了一个新的移码突变。在第三个CHS患者的淋巴母细胞样mRNA的北方印迹中发现了缺失（编码结构域的核苷酸3073和3074），（类似于13.5kb），而小mRNA的丰度没有减少。这些结果表明，单独的小亚型不能补充Chediak-Higashi综合征。
Chediak-Higashi syndrome is an autosomal recessive, immune deficiency disorder of human (CHS) and mouse (beige, bg) that is characterized by abnormal intracellular protein transport to, and from, the lysosome, Recent reports have described the identification of homologous genes that are mutated in human CHS and bg mice, Here we report the sequences of two major mRNA isoforms of the CHS gene in human and mouse. These isoforms differ both in size and in sequence at the 3' end of their coding domains, with the smaller isoform (similar to 5.8 kb) arising from incomplete splicing and reading through an intron. These mRNAs also differ in tissue distribution of transcription and in predicted biological properties, Novel mutations were identified within the region of the coding domain common to both isoforms in three CHS patients: C-->T transitions that generated stop codons (R50X and Q1029X) were found in two patients, and a novel frameshift mutation (deletion of nucleotides 3073 and 3074 of the coding domain) was found in a third, Northern blots of lymphoblastoid mRNA from CHS patients revealed loss of the largest transcript (similar to 13.5 kb) in two of seven CHS patients, while the small mRNA was undiminished in abundance, These results suggest that the small isoform alone cannot complement Chediak-Higashi syndrome.