A NOVEL HEMOPHILIA-B DEFECT DUE TO PARTIAL DUPLICATION OF THE FACTOR-IX GENE
A NOVEL HEMOPHILIA-B DEFECT DUE TO PARTIAL DUPLICATION OF THE FACTOR-IX GENE
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DOI：
10.1111/j.1365-2141.1994.tb04792.x
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发表时间：
1994-03-01
影响因子：
6.5
通讯作者：
CHAN, TK
中科院分区：
文献类型：
--
作者：
CHAN, V;AU, P;CHAN, TK
发现患有轻度FIX缺陷的患者具有基因的3'区域的部分重复，除了正常基因之外，还产生另一段含有外显子5'、6 '、7'和8'以及间插序列的DNA。连接区的克隆和测序显示，一条染色体/染色单体的3'非翻译区nt 31927和另一条染色体/染色单体的内含子4 nt 10640处发生交换。在交叉区域中未观察到同源性或拓扑异构酶特异性序列。对患者淋巴细胞的非法FIX转录物进行PCR和测序，结果显示至少有三种不同种类的mRNA。翻译这两个“新”的mRNA应导致截短的蛋白质。成熟mRNA剪接的可能性被提供来解释正常大小的FM蛋白的翻译，这是在Western印迹分析中证明的唯一产物。
A patient with mild FIX deficiency was found to have partial duplication of the 3' region of the gene, giving, in addition to the a normal gene, another piece of DNA containing exons 5', 6', 7' and 8' and the intervening sequences. Cloning and sequencing of the junction region revealed that crossover occurred at nt 31927 in the 3' untranslated region of one chromosome/chromatid and nt 10640 in intron 4 of the other. No homology or topoisomerase specific sequences were observed in the crossover region. PCR and sequencing of illegitimate FIX transcripts from the patient's lymphocytes showed at least three different species of mRNAs. Translation of two of these 'novel' mRNAs should result in truncated proteins. Possibilities for the splicing of the mature mRNA are offered to explain the translation of a normal-size FM protein, which was the only product demonstrated on Western blot analysis.